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Reviewed by Pete Nastasi, Certified Sports Nutrition Coach and Advanced Clinical Weight Loss Practitioner

Make sure to talk to a healthcare professional about your individual needs and appropriate dosages before adding a supplement to your routine.

Meal replacement shakes have come a long way in the past few years, with a greater variety of options than ever before. Thanks to advances in exercise science, wellness and the medical community, the list of promising products from start-ups and lesser-known manufacturers continues to grow, and established products keep getting better. If youve never tried meal replacement shakes before, the sheer number of options can be intimidating. So were here to help by explaining everything you need to know before choosing the best options for your lifestyle.

Meal replacement shakes consist of macronutrients such as carbohydrates, proteins and fats that are coupled with micronutrients such as essential vitamins, minerals and various plant compounds. Together, these elements make up a complete, on-the-go meal. Meal replacement shakes can be a good option for those with busy lifestyles; whether you are dealing with a demanding work schedule, shuffling kids to and from sports practice, or traveling, it can be hard to find time for a sit-down meal. Still, that doesn't mean you need to neglect your health to fuel up. If youre looking to avoid the fast-food line but still want to consume something easy and quick, consider adding a meal replacement shake to your routine.

Because meal replacement shakes supply a full meal, it's important to understand your health goals and needs, then select an option best suited to helping you achieve them. In addition, it is always advised that you work with a trained medical professional when implementing new dietary choices and supplements.

For those looking to bulk up or maintain weight during periods of heavy exercise, meal replacement shakes offer complete macro and micronutrients. Some people use meal replacement shakes as sustenance between meals or as a pre-or post-workout, to satisfy the body's need for additional energy. That being said, its important to differentiate between meal replacement shakes and protein shakes or powders as they are not the same thing.

Protein powders tend to be heavier on protein and lighter on carbs, fats, fiber and some vitamins and minerals. They are designed to aid in muscle repair and muscle gain during pre-and post-workout sessions or to act as a high-protein source for those consuming a low- or no- animal protein diet (such as vegetarians and vegans). Meal replacement shakes and powders, by contrast, supply nutrients to help you attain adequate daily values of both macros and micros.

Not all meal replacement shakes are created equal and it can be difficult to find one that checks all the boxes. Here are the best meal replacement shakes, broken down by specific categories to make it easier to find exactly which is best for you.

Transparent Labs

Transparent Labs has gone the extra mile to create a complete lineup of powders and supplements to support every aspect of your health and wellness goals from muscle building to mental clarity to joint support. As the name suggests, Transparent Labs publishes a detailed lab breakdown, called a certificate of analysis, for every product, and certificates of composition for most products on its website. The Meal Replacement powder contains 24 grams of protein from whey protein isolate and concentrate, grass-fed beef bone broth, egg white protein and pea protein. This powder contains 7 grams of fat, mostly from MCT (medium chain triglyceride) oil. The 19 grams of carbohydrates are derived from natural cane sugar and quality sources like pea starch and oat bran fiber, which also provide 5 grams of natural fiber.

This balance of slow and fast-burning macros from quality sources makes Transparent Labs a great choice to keep your body moving through a busy schedule or a tough workout. If theres one drawback, its that Transparent Labs lacks a substantial array of vitamins and minerals from whole-food sources. A dose of vegetable or other plant-based powders would go a long way to make this meal replacement shake truly complete.

For those already eating a well-rounded diet full of vitamins, minerals and other plant-based compounds, Transparent Labs is a well-made meal replacement powder designed to increase muscle repair and building and provide lasting energy for an active lifestyle.

Transparent Labs Meal Replacement Powder ($59.99 for approximately 56 oz. of powder; $2 per serving)

Kaged

Kaged Clean meal replacement powder is packed full of dense nutrients from various whole food sources. But what makes this powder unique is the brands trademarked ioWhey protein isolate. According to Kaged, ioWhey technology increases the surface area of the protein molecules for up to 123% better bioavailability than traditional whey powders. This powder delivers 28 grams of bioavailable protein from both the ioWhey and organic quinoa, containing all nine essential amino acids. Quinoa is also a good source of natural antioxidants, carbohydrates, fiber and minerals.Complemented with 18 grams of slow-burning carbohydrates mostly derived from oat flour, this powder is designed to keep you fueled through a tough workout or a busy day. With the addition of MCT coconut oil powder, which provides 4.5 grams of healthy fats, Kaged is a well-rounded macronutrient powder. Kaged Clean Meal goes a step further by adding a blend of vegetable and plant powders to supply ample whole food-sourced vitamins and minerals.

This blend contains a few common veggies, like broccoli and spinach powders and a handful of less-common superfoods such as kelp and maitake mushroom powders. This shake is a bit low on fiber (only 2 grams) and does contain sucralose.

Despite these downfalls, if you're someone with a very active lifestyle that demands a higher macronutrient intake, this is an excellent choice.

Kaged Clean Meal Replacement Powder ($49.99 for 41.34oz of powder, $2.50 per serving)

Iconic Protein

Iconic's line is ready to drink and packs a substantial amount of goodness into a relatively small 11.5-ounce bottle. These drinks are free from gluten, soy, GMOs, lactose, hormones, pesticides, corn, and carrageenan. They even come in a BPA-free bottle. Iconic uses a grass-fed milk protein isolate that provides 17 total amino acids, including nine essentials, for a healthy dose of 20 grams of protein per bottle.

The brand uses natural flavors, including real cacao powder and Colombian coffee, to produce flavors that taste clean and authentic. Their products are sweetened only with monk fruit and stevia, making these a zero sugar beverage. The Cacao + Greens option includes a full daily serving of veggies from kale, broccoli and spinach powders.

Iconic Protein Drinks ($39.99 for a dozen 11.5 oz. bottles (also available in 24 and 36 packs); $2.90 to $3.30 per serving, depending on case size)

Garden of Life

Garden of Lifes ingredient list reads more like a grocery list, with the majority of the nutrients derived from whole foods. Additionally, these ingredients are sproutedthe seeds and legumes are soaked in water for 24 hours and then allowed to start growing, which removes the phytic acid, a compound found on all seeds and legumes that interferes with calcium, iron and zinc absorption. And since the ingredients are processed at low temperatures to maintain the "raw" designation, the 28 grams of proteins per serving remain intact. The brand claims that this makes them fully absorbable for maximum muscle building.

This meal replacement shake also serves up 8 grams of naturally-occurring plant fiber per serving and no added sugars for a total of 10g of carbs (2 grams net carbs). In addition to the basic macros and micros, Garden of Life has added some unique superfoods that it claims can boost overall health, such as cinnamon, which it says helps to stabilize blood sugar, and ashwagandha, which it says can help reduce the effects of stress.

In addition to the superfoods, this product also contains a raw probiotic and enzyme blend that contains two Lactobacillus strains and 13 enzymes that may aid overall digestion.

Garden of Life Raw Organic Fit ($39.19 for 14.4 oz. of powder or $49.59 for 32 oz. of powder, $2.50 per serving)

Field Work

Field Work Nutrition is new to the game, but it came ready to play. Co-founded by a premier endurance coach, it utilizes a substantial variety of whole foods and superfoods to make this meal replacement shake a powerhouse of vitamins and minerals. Two such thoughtfully added ingredients are curcumin and tart cherry, which the brand says can control and reduce inflammation in the body.

Field Work has also added a robust fruit and vegetable blend to supply micronutrients. These naturally occurring vitamins and the added natural sea salt supply a healthy dose of the minerals essential for electrolyte balance (sodium, calcium, magnesium, and potassium). A pre-and probiotic blend has also been added to support gut health and a digestive enzyme complex to support digestion and absorption of the nutrients in the smoothie.

To make this a complete meal replacement product, Field Work has included 20 grams of protein from grass-fed whey and milk protein concentrate as well as 5 grams of fat from coconut oil powder and 18 grams of carbohydrates. The majority of the carbohydrates come from high-quality sources like sweet potato, oats, amaranth, chia and quinoa, making them slow-burning for sustained energy.

This meal replacement shake is excellent for anyone who has difficulty consuming enough plant foods regularly or anyone looking for a superfood boost from a meal replacement shake.

Field Work Nutrition Primo Smoothie ($55 for 33 oz. of powder, $3 per serving)

Orgain

Orgain is the brainchild of cancer-survivor turned-integrative-medicine-specialist, Doctor Andrew Abraham.

This shake uses USDA organic ingredients and is free from artificial sweeteners, flavors, preservatives, soy, gluten, GMOs and carrageenan. Its also free from dairy and lactose, and is vegan-friendly. Instead of the grass-fed milk protein found in most of Orgains other products, the 20 grams of proteins in this powder come from organic peas, brown rice and chia seed. It also contains complex carbohydrates from a sprouted blend that includes various seeds and beans like amaranth, quinoa, garbanzo, flaxseed and pumpkin seed.

Orgain also included a greens blend and a fruit and vegetable blend, which it says ensures this meal replacement shake supplies adequate micronutrients and beneficial plant compounds. In total, these all add up to 25 grams of carbohydrates. Orgain makes a great product suitable for anyone with common food sensitivities or allergies.

Orgain Organic Meal Powder ($39.99 for 32 oz. of powder with discounts on subscription service; $2.50 per serving (or $1.87 per serving with a subscription)

Ample

Ample traded out the whey protein in its Original Meal Shake for pea protein to make this vegan-friendly meal replacement shake. And, perhaps knowing how difficult it can be for vegans to consume enough complete proteins and good fats due to dietary choices, Ample loaded this meal replacement shake with macros to support health and body functions.

For starters, there are 26 grams of fatderived mostly from coconut oil (with some from macadamia nut oil). The high fat content means you will likely feel more satiated with your liquid meal, allowing you to go a longer period of time between meals. It also means that your body is getting a healthy dose of the saturated fats essential for cellular health and hormone production that can be hard to consume in adequate amounts with a plant-based diet.

The remainder of the ingredients in this product are non-GMO and from whole-food sources. The 20 grams of protein in Ample V come mostly from organic peas. And this protein is a high-quality source of essential amino acids and one of the better choices for a vegan-safe protein, as it is a complete protein. The carbohydrates in Ample V come mostly from whole grain oat powder. This, coupled with the acacia fiber and vegetable powders, makes for a fiber-rich shake at 11 grams per serving.

Ample has also added a healthy dose of probiotics for gut health and a few vegetable powders to supply vitamins and minerals. Though, it could probably do with adding a few more plant powders to boost the overall nutritional content, but still this shake makes an excellent choice for vegans or anyone preferring plant protein.

Ample V ($4.50 to $6 per serving, depending on the package)

HLTH Code

For those who follow the high fat, low carb ketogenic diet, HLTH Code makes an excellent option.

HLTH provides 27 grams of protein from whey protein concentrate, grass-fed collagen and egg whites. The addition of collagen is particularly great because collagen is essential for maintaining the health of connective tissues (tendons and ligaments), joints and skin. An active lifestyle can stress connective tissues and joints, so a collagen boost is especially welcomed. HLTH also provides 27 grams of fat from coconut oil powder, olive oil powder, MCT powder, flaxseed, cocoa butter and grass-fed ghee far and away the most diverse and superior fat sources on our list of meal replacement shakes. HLTH has 13 grams of carbohydrates with 9 grams from soluble vegetable fibers, for only 4 grams net carbs to keep you within your daily carb limit.

HLTH also includes a significant amount of real, mineral-rich sea salt. This is valuable because people on the keto diet often have lower sodium levelstheyre generally not able to eat high-sodium packaged foods that are common in many peoples diets, and clearing ketones also causes the body to lose sodium. Despite containing none of the vegetable powders that we see in most meal replacement shakes, HLTH has still managed to create a powder thats rich in 25 vitamins and minerals due to the nutrient-dense ingredient list. This meal replacement shake is thoughtfully made and an excellent choice for those following the keto diet or anyone looking to lower carbohydrate intake and increase fat intake.

HLTH Code Complete Meal ($59.95 for a 42 oz. bag with a discount for the subscription service; $4 per serving ($3.33 per serving with subscription)

Your meal replacement shake should contain high-quality, complete protein from sources like grass-fed whey, egg whites, beans and seeds. Whey protein is one of the most popular protein sources in meal replacement shakes because it is highly absorbable and contains all nine essential amino acids. Pea protein, derived from yellow split peas, has become one of the leading sources of high-quality plant-based proteins commonly used in meal replacement shakes. Both whey and pea proteins contain all nine essential amino acids, making them complete proteins and highly effective for muscle repair and growth. The amount of protein you aim for will vary based on your overall diet and goals. A good starting point for many people is around 20-25 grams of protein per shake, which has been shown to stimulate muscle building.

You should avoid meal replacement shakes with protein from wheat. These are low-quality sources of protein that lack essential amino acids, rendering them mostly ineffective for muscle repair and growth.

Healthy fats, usually polyunsaturated and monounsaturated fatty acids, are found in certain vegetable oils, nuts and seeds among others, and can provide some benefits for the body such as decreasing your risk for disease. Its wise to avoid hydrogenated oilsthey contain trans fats, which can increase your risk of developing heart disease and other health problems.

Carbohydrates are great for supplying the body with energy. However, if they come from simple sources like corn, that energy is likely to burn out quickly, leaving you feeling like a car without gas. Complex carbohydrates such as oat powder, sweet potato flour and various bean or seed powders are digested more slowly by the body for a more sustained energy supply. These carbohydrates also contain fiber, which aids in digestion and helps you feel fuller for longer.

While it's important that your meal replacement shake tastes delicious, it's far more important that you don't compromise your health by settling for a powder loaded with sugar or artificial sweeteners. Traditional sugar may appear on the label in different names like dextrose, fructose or corn syrup solids. Beware that all of these sugars will cause your blood sugar to spike.

It's equally important to read the label for artificial sweeteners, such as aspartame and sucralose. These ingredients have been linked to cancer and other chronic diseases, supported by the Journal of Pharmacology & Pharmacotherapeutics. Instead, look for a meal replacement shake with low sugar content (4g maximum) from healthy sources, such as maple or coconut sugar or a version that uses a natural plant-based sweetener such as monk fruit to boost the taste.

Probiotics, often in the form of cultures similar to what you see in yogurts or other fermented products, are necessary to keep your gut microbiome healthy. Prebiotics are indigestible plant fibers that act as food and nutrients for your gut microbiome. Sources in meal replacement shakes often come from inulin (usually from chicory root fiber). A healthy gut is important for overall health and good digestion. When your gut is not functioning properly, it inhibits the absorption of both macro and micronutrients, rendering your food (and your meal replacement shake) virtually ineffective.

Vitamins and minerals are used as coenzymes and cofactors for many of the metabolic reactions in the bodymeaning, your body needs them to complete the processes that transform food into energy. This is why it is important to eat a wide variety of foods to ensure you are getting these micronutrients into your body through your diet. If necessary, a meal replacement powder with some added micronutrients can help you fill in some of the gaps where you might be deficient. A good rule of thumb is to check the ingredient list for vegetables, fruit, mushroom and other plant powders if you are looking to round out your meal replacement shake.

While some people have been diagnosed with food sensitivities or allergies, many people are unaware that they have any issues. If you commonly feel bloated, have gas or have other digestive issues, you may be sensitive to common allergens. If this is the case or if you have been diagnosed, you may want to steer clear of products containing lactose, gluten, wheat or soy. Keep in mind that most whey proteins contain lactose (some may contain trace amounts of gluten if they are not 100% pure). If you have true sensitivities or allergies, read the label closely for certified claims about being allergen-free. Look to see if the product was made in a facility that processes nuts, soy, or other allergens, and check for NSF Certified Gluten Free, Non-GMO Project Verified, and USDA Organic badges, depending on your sensitivities.

If you recognize most, if not all, of the ingredients, thats a good sign you have a quality product. Poorly made products contain food chemicals to improve the texture and stability of the shake. Some shakes contain synthetic vitamins as a cheap alternative to whole or real foods. Others contain fillers. These are products with little-to-no nutritional value but they act as bulk to add weight to the bottle. Thickeners are used in some meal replacement shakes to help create a more consistent texture once the liquid is added. Carrageenan is a very common thickener that, while derived from natural seaweed, has been linked to gastrointestinal damages, including "mucosal erosions and ulceration," according to Environmental Health Perspectives.

Its imperative that you have a clear vision of the health goals you are aiming to achieve, so you can select a product to help you hit the mark. Are you someone who is using a meal replacement shake to bulk up? If so, you'll want much higher macronutrients than someone trying to slim down or maintain weight.

Suppose you are using a meal replacement shake because you don't always have time or the ability to eat a meal. In that case, you'll want to choose a balance of macros and a healthy dose of micronutrients to act as a sound substitute for a meal. Know your goals and choose a powder accordingly. If you are uncertain about your goals, reach out to a health professional to learn more.

Unless you choose a ready-to-drink meal replacement shake, you'll want to invest in either a blender or a shaker bottle. Simply stirring your meal replacement powder into liquid will only leave you with a lumpy, inedible (or undrinkable) drink. Blenders are great for when you're at home and have an extra minute to mix your drink. You can always throw in some fresh greens or fruit and ice to make your meal replacement shake into a smoothie for added nutrition and flavor. But if youre on the go, a shaker bottle is an easy way to keep your drink blended and smooth.

The time you drink your meal replacement shake can vary based on what works best for your schedule. Most people replace just one meal per day with one of these shakesgenerally whatever meal is most convenient for you. However, If you are considering replacing multiple meals with a meal replacement shake then we strongly urge you to discuss it with your qualified health care provider.

You can drink a meal replacement shake between meals or before or after workouts to increase caloric and nutrient consumption (for those trying to increase muscle mass and body weight). If you just need something to fill in occasionally, you can keep a stash of meal replacement powder in your desk drawer or your gym bag and just add water when you find yourself in a bind and unable to eat a meal. Just keep in mind that the powder for these shakes could be affected by temperature and climate fluctuations such as humidity which can cause the powder to clump up.

While whole food meals are usually our best option, busy schedules dont always allow for this luxury. Whether you are trying to bulk up, lean out or just get through your busy day, you can consider a meal replacement shake to aid your health and fitness journey.

Well-made meal replacement shakes are more nutrient-dense and contain much more of the healthy ingredients your body needs than a lot of the alternative on-the-go options such as fast food or candy bars. Once you know what fuels your body and what meal replacement shake is best suited to meet your dietary needs, you can confidently choose the right product to help you reach your goals and keep you on the move.

Prices are accurate and items in stock at time of publishing.

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The Best Meal Replacement Shakes of 2022 - Sports Illustrated

Clients now view these services as essential for geriatric patients, canine athletes, and pets recovering from certain surgeries

Rehabilitation services are emerging in veterinary medicine in parallel with the specialty and formal training most recently recognized by the American Veterinary Medical Association, the American College of Veterinary Sports Medicine and Rehabilitation.

At the 2022 Fetch dvm360 conference in Charlotte, North Carolina, presenter Janice L. Huntingford, DVM, DACVSMR, MS-TCVM, CVA, CVPP, CCRT, also explained that clients now view these services as essential for geriatric patients, canine athletes, and pets recovering from certain surgeries.1 Along with this, she shared key reasons that integrating rehabilitation including a range of therapeutic exercise and modalities (eg, hydrotherapy, ulstrasound, etc) would be especially advantageous for your practice.

Rehabilitation provides a unique service because the goals of treatment are functional and created specifically for patients who need to improve their movement or quality of life where other methods solely may not prove effective.

Huntingford illustrated an example in a dvm360 interview: So if you have a dog who has difficulty walking, it's already had its cruciate repaired but it's still not walking, it may be because its muscles are painful. And rehabilitation allows you to take those dogs and and create a scenario where they're able to walk again, because you're really dealing with functional things like that.

According to Huntingford, rehabilitation is ideal for geriatric canine patients because they typically have various health problems and medication cant address all of them. Additionally, these dogs often have stomachs that are sensitive to drugssuch as non-steroidal anti-inflammatorieswhen they are in pain because of arthritis. Thus, you can use rehabilitation methods as nondrug therapies for them.

A small animal practitioner may want to start doing rehabilitation because it gives them more tools in their toolbox when treating dogs that are geriatric who have pain and mobility issues, Huntingford said, in the interview.

Because many of these dogs have problems taking conventional drugs, either they're vomiting or they get diarrhea or they have kidney disease, and they just can't take it but they still need to have their pain managed, they need help with mobility. So in that case, you can do rehabilitation techniques [such as] therapeutic exercises, joint mobilization, hydrotherapy, laser, acupuncture . . . so it allows you to continue to treat your patients, she added.

Furthermore, engaging in rehabilitation medicine bonds you with patients, but with clients as well. Huntingford said that pet owners are often grateful that you are treating their older patients, those recovering from surgery and all others in need of an alternate therapy. It is appreciated by them that you are helping their pets pain to be better managed.

Reference

Huntingford J. Integrating rehabilitation into a busy general practice.Presented at: Fetch dvm360 Conference; April 22-24, 2022; Charlotte, North Carolina.

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Benefits of integrating rehabilitation into your practice - DVM 360

By Dr. Rajesh R

The World Retinoblastoma Awareness Week is observed every year in May. This year it falls between May 8-14, when healthcare providers around the world come together to create public awareness about retinoblastoma. It is the most common and life-threatening eye cancer in children, less than five years of age. It can affect any socio-economic group without any racial or gender preference. It can affect either one or both eyes. It is a type of eye cancer that begins in the retina the sensitive lining inside the eye. It is quite rare and is usually caused by a genetic mutation that makes the cells in the eye multiply rapidly and thereby forming an abnormal growth. With improved techniques, the survival of children with Retinoblastoma has improved but low awareness is still a cause of concern. Hence early detection and treatment is vital to control the malignant growth, thereby saving the vision and childs life.

Every year, almost 1 in 10,000 live births in the world has retinoblastoma and India has been proposed to have 3 times this global average and recorded as the highest number of affected children in the world. While the survival rate for retinoblastoma is over 95% in the developed countries, it is around 40-75% in developing nations like India due to a combination of multiple factors like poverty, illiteracy, lack of awareness, delay in seeking medical attention, and lack of access to healthcare resources. The care of retinoblastoma children during the pandemic was challenging as the nationwide lockdown had deprived retinoblastoma patients of optimal management. The entire impact of the pandemic on retinoblastoma management is still not known, but it is important to increase awareness of the timeliness of diagnosis and treatment.

SYMPTOMS

Some early cancers may have signs and symptoms that can be noticed, but that is not always the case. At early stages, the symptoms might be very subtle due to which the child may seem fit, but delay in diagnosing retinoblastoma can lead to advanced stages at presentation which may necessitate prompt removal of the affected eye. The most common presentation of this disease is with abnormal light reflex white eye, or cats eye reflex noted usually by neighbours or relatives. This is easily identified using flashlight photography seen as a white reflex. Crossed eyes or squint, swelling, irritation and endless watering are other common symptoms. The vision is lost rapidly and the child might frequently bump into objects and get hurt. There are other eye diseases which may present with similar signs and symptoms as retinoblastoma. This has to be confirmed after evaluation by an ocular oncologist.

DIAGNOSIS &TREATMENT

When diagnosed early there is good chance of both vision and eye-ball preservation. In some cases, when diagnosed late, the eye-ball might have to be removed to prevent spread of the cancer in the whole body. Scans and other imaging tests can help your childs doctor determine whether retinoblastoma has grown to affect other structures around the eye. With advanced chemotherapy techniques and local forms of therapy, we are able to preserve vision also in many cases. Retinoblastoma requires multidisciplinary coordinated care, and it requires involvement of multiples specialties, including ophthalmology, oncology, radiology, genetics, anaesthetist and others.

PREVENTION

Since retinoblastoma is inherited mostly from the genes, there are no fixed measures of prevention. But keeping optimal care of your eyes on a regular basis may help reduce the risk. Awareness on retinoblastoma is very crucial, especially when the world is amidst a pandemic. Many patients have reported eye infections post-covid and that should not be neglected. Eye infections might look like a small issue, but if not treated can turn fatal, hence we should always indulge in regular medical check-ups, particularly for children as precaution is always better than cure.

It is important to note that there is a chance of the cancer returning even after completing the treatment for retinoblastoma. Furthermore, children who have inherited this genetic mutation have a high chance of developing cancer in other parts of their body as well, hence regular follow-ups and screening is essential.

(The author is Consultant, Vitreoretina and Ocular Oncology Sankara Eye Hospital, Bangalore. The article is for informational purposes only. Please consult medical experts and health professionals before starting any therapy, medication and/or remedy. Views expressed are personal and do not reflect the official position or policy of the FinancialExpress.com.)

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Retinoblastoma among children: Early detection and treatment are vital - The Financial Express

Perceive Biotherapeutics is focused on the discovery and development of transformative gene therapies and other therapeutics for ocular diseases with high unmet need. By leveraging deep genetic understandings, Perceive Bio researchers have discovered key protective biological targets that uniquely position the Company to accelerate the development of best-in-class therapies for programs that represent over 50% of currently untreatable causes of blindness. Perceive Bio is advancing therapeutic programs in AMD, glaucoma, and additional undisclosed disease areas.

"Dr. Anne Fung is a unique force in clinical leadership," said K. Angela Macfarlane, CEO of Perceive Biotherapeutics. "She is dedicated to advancing science to help patients preserve their vision. As a practicing retinal specialist, Anne ran both investigator-sponsored and industry-sponsored multi-center trials prior to joining industry. We believe Perceive Bio's pipeline of ophthalmic drugs and technology platforms, complemented by Anne's leadership, positions us to transform care with protective therapeutics."

"We look forward to collaborating with Anne and the Perceive Bio team," said Jeffrey S. Heier, MD, Director, Retina Research, Ophthalmic Consultants of Boston, and member of the Perceive Bio Medical Advisory Board. "Her success in developing and launching novel, groundbreaking therapies in ophthalmology is well recognized. Genetically informed, sustained therapies are important and have the potential to have meaningful impact in our spectrum of patient care."

Dr. Fung joins Perceive Biotherapeutics following eight years of leadership at Genentech, a member of the Roche Group. During her tenure, she led the US Medical Affairs Ophthalmology team to advance clinical research in AMD, diabetic eye disease and other ocular conditions with an expansion from Lucentis to lampalizumab (GA), faricimab (DME/AMD) and the Port Delivery System (AMD/DME/DR). In 2019, she was selected to become the Global Development Lead for the Port Delivery System, where she led the team through key aspects of development and through Phase 3 trials of the first long-acting neovascular AMD therapy which received FDA approval in 2021 (SUSVIMO). Over two decades, Anne has pursued a passion for research of age-related macular degeneration and ophthalmology in academic, private practice, and biotech industry settings with US and global collaborators. Her research spans RPE transplantation, cataract biology, real-time OCT imaging observations of the effects of anti-VEGF on neovascular AMD and clinical applications of Lucentis globally, resulting in multiple publications, presentations and book chapters that have helped shape the current practice of care for neovascular AMD globally.

Dr. Fung is active in medical retina clinical practice in San Francisco and serves as the Research Chair for the Ophthalmology resident research program at California Pacific Medical Center. A graduate of Wellesley College and Cornell University Medical College, Anne completed her Ophthalmology residency at Stanford University Medical Center and a fellowship in Medical Retina at the Bascom Palmer Eye Institute in Miami.

"I have been passionate about retinal research and finding new solutions for over 20 years," said Dr. Fung. "I see the key pieces of science coming together at Perceive Bioto bring even more hope and vision to patients around the world."

About Perceive Biotherapeutics

Perceive Biotherapeutics is advancing a deep and diversified pipeline of targets and treatment modalities in multiple therapeutic verticals, with lead pipeline programs in ophthalmology. Perceive was founded on compelling research elucidating two novel protective biologies for treating retinal blindness, developed from foundational collaborations in genetic science and target validation. The Company is backed by Deerfield Management and will be raising a Series B later this year. For more information, please visit http://www.perceivebio.com

SOURCE Perceive Biotherapeutics, Inc.

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Perceive Biotherapeutics Appoints Anne E. Fung MD, as Chief Medical Officer to Drive Transformational Clinical Programs - PR Newswire

Findings from First-in-Human Study Support Continued Clinical Development of Investigational IOP-lowering Therapy; New Trials Planned as Complementary Glaucoma Treatment and in Rare Pediatric Indication

WELLESLEY, Mass., May 18, 2022--(BUSINESS WIRE)--Qlaris Bio, Inc. (the "Company" or "Qlaris"), a biotechnology company targeting high unmet needs in debilitating ophthalmic diseases, today announced results from QC-201, a first-in-human, Phase 2 clinical trial of QLS-101, the Companys investigational therapy for lowering intraocular pressure (IOP) in the treatment of glaucoma. Study findings demonstrated a favorable safety and tolerability profile for QLS-101, including no evidence of hyperemia (eye redness), as well as a positive efficacy signal, in patients with primary open-angle glaucoma (POAG) or ocular hypertension.

These data support the ongoing clinical development of QLS-101 and Qlaris intends to initiate several new studies designed to further assess the potential role of the compound as a first-in-class glaucoma treatment. Additional clinical trials will seek to evaluate QLS-101 as a complementary therapy to available glaucoma treatments and procedures, such as prostaglandin analogs and minimally invasive glaucoma surgery (MIGS), and as a treatment for juvenile patients with Sturge-Weber syndrome (SWS)-related glaucoma.

QLS-101 is a novel adenosine triphosphate (ATP)-sensitive potassium (KATP) channel modulator administered as a topical eyedrop. Unlike currently available therapies for lowering IOP in glaucoma, QLS-101 targets distal outflow resistance and episcleral venous pressure (EVP), a key component of IOP. QLS-101 improves the outflow of aqueous humor by widening outflow channels and the episcleral vessels of the eye distal to the trabecular meshwork to lower IOP.

"These Phase 2 data are encouraging, particularly the absence of hyperemia, which is a common side effect with certain glaucoma treatments and one which can lead patients to discontinue therapy," said Thurein Htoo, MS, MBA, chief executive officer and co-founder of Qlaris Bio. "With the well-tolerated safety profile and efficacy signal demonstrated in this study, we believe QLS-101 can serve as a compelling complement to existing drugs and drainage devices to help patients for whom EVP and distal outflow resistance may be pathologic or treatment-limiting."

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"As a clinician, I often see glaucoma patients whose vision loss continues to progress even when treated with current therapeutic options that target different components of IOP than EVP," said Barbara Wirostko, MD, FARVO, chief medical officer and co-founder of Qlaris Bio. "QLS-101 may provide a first-in-class mechanism of action to lower IOP by focusing on resistance distal to the trabecular meshwork of the eye that is not yet fully addressed by available therapies. We look forward to initiating additional studies pursuing these new solutions."

POAG is the most common adult form of glaucoma and remains one of the leading causes of preventable blindness worldwide. Elevated IOP remains the only modifiable risk factor for progression of glaucoma. Despite available therapies and surgical interventions, patients with POAG may not achieve IOP-lowering goals as available options only target three components of IOP. This leaves the fourth component of IOP EVP insufficiently addressed.

"The results from the QC-201 trial are promising and certainly should prompt continued study of the potential impact of this promising investigational therapy," said Sharon F. Freedman, MD, professor of ophthalmology and pediatrics at Duke University Medical Center, and a principal investigator in ongoing Qlaris trials. "An EVP-targeting therapy could also address a significant unmet need for patients living with certain types of glaucoma, such as Sturge-Weber syndrome. I look forward to continued collaboration with Qlaris on this important work."

SWS is a pediatric rare disease signified by a facial port wine birthmark. Individuals living with SWS often suffer from severe, intractable glaucoma in the eye on the same side as their birthmark. In these individuals, increased IOP is driven by pathologically elevated EVP. By directly lowering EVP, QLS-101 may be uniquely well-suited to address SWS and improve therapeutic outcomes.

About QLS-101

QLS-101, Qlaris Bios lead product candidate, is a prodrug of levcromakalim, an adenosine triphosphate (ATP)-sensitive potassium (KATP) channel modulator. By lowering episcleral venous pressure (EVP) and increasing aqueous humor outflow through vessels distal to the trabecular meshwork, QLS-101 may be able to uniquely address diseases of pathologic EVP resulting in elevated intraocular pressure (IOP), such as Sturge-Weber syndrome-related glaucoma, and diseases where EVP limits maximal therapy, including primary open-angle glaucoma and normal-tension glaucoma. QLS-101 was invented at Mayo Clinic and the University of Minnesota and is being developed under an exclusive worldwide license.

About Qlaris Bio, Inc.

Qlaris Bio, Inc. was founded in August 2019 with a singular focus: to develop novel, innovative therapies with first-in-class mechanisms of action to address serious and debilitating ophthalmic diseases. The companys lead platform is based on the use of adenosine triphosphate (ATP)-sensitive potassium (KATP) channel modulators to affect the tone of vascular and vascular-like tissues, initially focused on ophthalmic use. Qlaris Bios investors include Canaan and New Leaf Venture Partners, both of which were co-lead investors in the companys $25 million Series A round in August 2019. Other investors include Correlation Ventures and Mayo Clinic. For more information, please visit qlaris.bio.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220518005187/en/

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Media Contact Matt Pera973-886-9150matt.pera@smithsolve.com

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Qlaris Bio Reports Phase 2 Clinical Trial Results Demonstrating Favorable Safety and Tolerability Profile and Positive Efficacy Signal for QLS-101 -...

Illustration by Brendan Totten

Helene Macedo didnt think about it much when her headache started around noon.

It was Oct. 26, 2020, and the nurse and case manager at Rhode Island Hospital was in the midst of a very busy Monday. Elective surgeries had resumed at hospitals around the state, but COVID-19 was still in full swing, and case numbers were beginning to creep toward a winter surge. Nursing homes were still seeing waves of infection, and Macedo was having trouble finding somewhere to discharge patients when they left hospital care. A nurse in the intensive care unit, operating room and recovery room for three decades before shifting to case management in 2018, she knew the importance of getting healthy patients out of the hospital quickly to free up beds for newer, sicker ones coming in.

There was a lot of pressure every day. You would come in, the rules would be changing everywhere in the state with COVID, and it was just a very stressful time, she says.

Fully masked and too busy to think about drinking water, she assumed she was dehydrated. It wasnt until she sat down for lunch around 3 p.m. that she knew something was wrong.

All of a sudden I started to eat and I was like, Oh my God, I cant taste my food. Panic set in, because especially then, that was the big thing. You lose your taste and smell, she says.

She immediately left for home to begin what she expected would be a two-week period of isolation and rest. A positive test the next day confirmed she had COVID-19. For the next few weeks, crippling headaches and fatigue like shed never before experienced kept her mostly confined to her bed. After about a month, the headaches began to subside, only to bereplaced by cardiac symptoms like chest pain and an elevated heart rate. A former marathon and triathlon runner who worked out six days a week, Macedo now found herself winded from walking to the end of her driveway. Tests revealed she had myocarditis, a swelling of the heart muscle seen in some patients with COVID-19, as well as pericardial effusion, a buildup of fluid around the heart.

As the weeks wore on, she began noticing other things. Simple tasks that were once routine now left her stumped and forgetful. Conversations were difficult to remember, and driving to her husbands workplace a short distance away from her Cranston home now proved impossible without GPS. Cooking, a favorite activity, became a minefield as she struggled to focus on simple recipes with no sense of taste to guide her.

To go from that level of functioning to literally barely making it through a day at home was just that was eye-opening, she says. It starts to play with your head a little bit.

Difficulty concentrating, chest pain and shortness of breath are all symptoms of what the Centers for Disease Control and Prevention calls post-COVID conditions, better known as long COVID. In January of 2021, Macedo began visiting Lifespans Long Covid Clinic for patients experiencing symptoms weeks or months beyond their initial infection. She took a leave of absence from work while following a regimen of physical therapy and medication to get back to her functioning self. Nine months after her initial positive test, she finally felt ready to return. She resumed her old job at Rhode Island Hospital in July 2021, starting off in four-hour shifts. Anything more, and the headaches would return, bringing with them the fatigue that forced her back to bed.

Every day that would go by that I was not able to go back to work I was getting more nervous and sad thinking, Oh my God, what if I dont return to work? she says.

Helene Macedo spent nine months away from her job at Rhode Island Hospital after contracting long COVID. Photography by Alex Gagne.

Macedos Story of anxiety, illness and a life disrupted by COVID-19 is familiar to those living through the front lines of the pandemic. Though most health care workers evaded the debilitating effects of long COVID, nearly all have faced the strain of working under the constant threat of a potentially life-altering illness, made real by the suffering of patients every day. For most, the toll has been not physical but mental as pandemic life brought years of stress and burnout beyond their breaking point, forcing front-line medical workers across the industry to adjust their lives as a result.

I feel like in medicine, its always a balance of wins and losses. You have this bucket thats about half-full all the time because if it was too full, it would bubble over, says Dr. Bradley Collins, a hospitalist at Miriam Hospital. With the pandemic, it was just constantly being at patients bedsides, holding iPads for them when they were dying so they could say their farewells to their family members, understanding that people couldnt visit because we had to try to keep the public safe. We didnt have those wins to sort of empty the bucket a little bit. I think it got to a point for some of us where that got so full, even little things would cause it to spill over.

Jacqueline Insana, a psychiatric nurse working in Rhode Island, describes the large number of patients in need of behavioral and mental health services as a second pandemic. As levels of anxiety and depression have increased nationwide, so too have the needs of providers who care for patients. Sometimes, she says, shell receive texts or phone calls from friends working in health care seeking advice regarding their own mental health where to find a therapist, or whether they should seek out professional help.

To go from that level of functioning to literally barely making it through a day at home was just that was eye-opening. It starts to play with your head a little bit. HELENE MACEDO

Nurse Karen Dreyer interacts with assistant nurse manager Emily Breguet in the neonatal intensive care unit at Women and Infants Hospital. Photography by Alex Gagne.

Probably a couple months in I saw a lot more nurses saying, Hey, Im not sleeping. Im struggling with this, Im not sure I can go to work anymore. Im crying on my way home; what are resources I can reach out to to make sure Im OK?

Dr. Nadine Himelfarb, an emergency medicine physician and president of the Rhode Island chapter of the American College of Emergency Physicians, has been studying burnout for more than ten years. The term is commonly attributed to Herbert Freudenberger, a New York psychologist who in the 1970s used it to describe the physical and emotional exhaustion among volunteers and workers at an addiction clinic, including himself. In 1981, Christina Maslach developed a scale for assessing burnout, establishing emotional exhaustion, depersonalization and a reduced sense of personal accomplishment as the three factors widely used to determine burnout in individuals. In her own view, Himelfarb says burnout is often the result of a values mismatch where someones experience of a job does not align with the reason they entered that field in the first place.

Everybody goes into medicine because of some version of I want to help people, she says. And what happens is you get into medicine, and you have to practice medicine within what has become the confines of the business of medicine, which is not always patient-centered. It is certainly not a system that oftentimes is set up to allow physicians to have the impact that they want or help people in the way that they see people need to be helped.

Himelfarb experienced this in the fall of 2020 when she took a three-month sabbatical. At the time, she was working sixty hours per week between her clinical and academic responsibilities. Combined with the daily realities of working through a pandemic undressing on the front porch after every shift to protect her immunocompromised husband and four children she soon realized she needed to make a change.

It was in August of 2020, and I realized that I was feeling this way. I had been working, I dont know, a bunch of shifts in a row, and then I knew that I had a week off and I had this vacation, she recalls. That weekend, I felt like I could hardly get out of bed. I just had no energy. I didnt know what was going on.

Despite her research into the subject, Himelfarb didnt immediately recognize her symptoms as burnout. It was only when she noticed they disappeared when she was no longer thinking about work that she realized she was experiencing what shed studied for so long.

The impact of burnout on physicians has been well documented. In a 2011 study, researchers found 45.8 percent of physicians surveyed reported at least one symptom of burnout, a number that increased to 54.4 percent in 2014. A 2017 follow-up study found burnout among physicians had decreased to 2011 levels, around 43.9 percent, but physicians were still more likely than the general population to feel burned out or be dissatisfied with their work-life balance. Likewise, physicians suffer from higher rates of suicide than the general population. Researchers estimated in a 2018 study that the physician suicide rate was twenty-eight to forty per 100,000, more than twice the general population rate of 12.3 per 100,000.

Kathleen Boyd is the director of the Rhode Island Medical Societys Physician Health Program, a resource set up in 1978 to assist physicians experiencing health issues, including psychiatric and substance use disorders. In 2021, the program had its busiest year to date, with thirty-ninereferrals. Many of those were for medical professionals experiencing burnout or health issues such as increased substance use, anxiety, depression and post-traumatic stress disorder. The spike came after an initial lull in 2020, which Boyd attributes to physicians not having the time to seek help during the early months of the pandemic.

I think one of the things that happened for front-line physicians was it was difficult to have time for self-care, she says. Everybodys flat out. Getting help is really about self-care, and you have to kind of fit that into your schedule. For many of the front-line people, there wasnt time for that.

The trend of medical professionals struggling with burnout or mental health issues is not unique to the pandemic. Among the most common reasons for burnout cited by physicians in surveys conducted both before and during the pandemic is too much time spent on bureaucratic tasks, including charting requirements and paperwork. Other factors include long hours, a lack of respect from administrators or colleagues, insufficient compensation and the expanded use of electronic health records for patient documentation.

Thats what we hear, Boyd says. I see thirty patients or fifty patients, and then I go home and have dinner and help my kids with their homework, and then I do my charting until midnight. And thats kind of whats burning people out. Its really hard to have that boundary around your work life and your home life. Its tough.

In nurses, too, the effects of burnout can be long-lasting. A 2021 survey by the American Nurses Foundation found 34 percent of nurses considered themselves not or not at all emotionally healthy, and 42 percent said theydexperienced trauma as a result of COVID-19. Twenty-one percent said they planned to leave their positions within the next six months, while another 29 percent were considering leaving.

Dreyer speaks with nurse Danielle Buzzell. Photography by Alex Gagne.

Boyd talks about how the application of business models to health care, including the introduction of productivity quotas, has changed the experience for professionals working in the industry.

Were in the business of caring for others, and if your capacity for compassion becomes crushed, its compassion fatigue. And your ability to connect with your patients is also crushed because youre only allowed ten minutes to connect with them, then whats left? I think there are an awful lot of physicians who are leaving the field. And nurses, too. Theres just a lot of people who are like, theyre done, she says.

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How the Pandemic is Taking a Toll on Rhode Island's Front-Line Health Care Workers - Rhode Island Monthly

WAKEFIELD, Mass.--(BUSINESS WIRE)--Myrtelle Inc. (Myrtelle or the Company), a clinical stage gene therapy company focused on developing transformative treatments for rare genetic diseases, today announced that it has entered into a worldwide exclusive licensing agreement with Rescue Hearing Inc. (RHI) to develop a novel gene therapy for DFNB8 genetic hearing loss. The low-dose recombinant adeno-associated virus (rAAV) gene therapy is intended to deliver a therapeutic TMPRSS3 (transmembrane protease, serine 3) gene by local administration directly to the inner ear. Mutation in the TMPRSS3 gene is the underlying cause of DFNB8 genetic hearing loss in humans. Across its gene therapy programs, Myrtelle utilizes direct administration of low-dose gene therapy to target key cell types involved in the disorder, thereby avoiding immune-related and off-target effects that can arise with high-dose gene therapy administration delivered systemically. This strategy, currently being developed for Myrtelles central nervous system (CNS) programs, can be leveraged to other therapeutic areas outside the CNS, including adjacent and related areas such as the ear where local gene therapy delivery is potentially advantageous for hearing loss disorders such as DFNB8.

We are excited to partner with RHI on this important potential gene therapy for patients with DFNB8 genetic hearing loss. The program will leverage Myrtelles core capabilities and augment our product opportunities to build on the proof-of-concept demonstrated by RHI and move toward the clinic to advance a novel therapeutic approach for patients with DFNB8 genetic hearing, said Mark Pykett, Myrtelle CEO, adding, The potential significance of this new therapeutic hearing loss strategy for patients and families is high.

Preclinical studies in the mouse model of DFNB8-mediated deafness have demonstrated that delivery of a wild type TMPRSS3 gene was able to promote hair cell and neuron survival and improve hearing function. Recently, a successful meeting was held with German health authorities and the Paul Ehrlich Institute to discuss clinical trial authorization (CTA) requirements for starting a first-in-human study. CTA-enabling nonclinical work is currently planned to start later this year to meet these requirements.

RHI is a private, preclinical stage gene therapy company focusing on diseases affecting human hearing. The DFNB8 program targets a common form of genetic hearing loss caused by a mutation in the TMPRSS3 gene. TMPRSS3 mutation is the most common form of genetic deafness in the adult cochlear implant population. DFNB8 patients experience progressive hearing loss usually starting in late teens and early 20s which can lead to complete deafness. RHIs initial preclinical research has demonstrated positive proof-of-concept data enabling entrance to the IND development phase.

We are pleased to partner with Myrtelle on this exciting program. Myrtelles team and their drug development experience are an outstanding fit for the TMPRSS3 AAV-based gene therapy program for DNFB8-related genetic hearing loss. The groundbreaking proof-of-concept data generated by our scientific team lead by Dr. Hinrich Staecker (University of Kansas Medical Center), Dr. Zheng Yi Chen (Mass Eye and Ear Infirmary), and Dr. Xue Zhong Liu (University of Miami Health System) provide a strong foundation for further development. The RHI team is proud to have brought the TMPRSS3 program to this exciting stage and look forward to advancing the program into the clinic with Myrtelle with the goal of developing a novel therapy to positively impact unmet medical needs of the genetic hearing loss community, said Jim Ayala, CEO/Founder Rescue of Hearing.

ABOUT MYRTELLEMyrtelle Inc. is a clinical stage gene therapy company focused on developing transformative treatments for neurodegenerative diseases. The company has a proprietary platform, intellectual property, and portfolio of programs and technologies supporting innovative gene therapy approaches for neurodegenerative diseases. Myrtelle has an exclusive worldwide licensing agreement with Pfizer for its lead gene therapy program in Canavan Disease. For more information, please visit the Companys website at: http://www.myrtellegtx.com.

RESCUE HEARING INCRescue Hearing Inc (RHI) is a private, preclinical stage gene therapy company focused on the genetic forms of hearing loss. RHIs initial product (RHI100) has produced positive proof of concept data and is entering the IND development phase. RHI100 targets a common form of genetic hearing loss caused by a mutation in the TMPRSS3 gene. TMPRSS3 mutation is the most common form of genetic deafness in the cochlear implant population. RHI has two additional gene therapy assets in development. For more information, please visit the companys website at: http://www.rescuehearing.com.

DFNB8Individuals with mutations in TMPRSS3 present with two phenotypes: DFNB10-associated hearing impairment that is pre-lingual and DFNB8-associated hearing impairment that is typically late-onset and post-lingual. TMPRSS3 mutations can be divided into mild or severe; the combination of two severe mutations causes profound pre-lingual hearing loss, whereas milder mutations lead to less severe post-lingual hearing loss.

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Myrtelle Enters into a Worldwide Exclusive License Agreement with Rescue Hearing to Develop and Commercialize Gene Therapy for the Treatment of...

The American Society of Gene and Cell Therapy (ASCGT) annual meeting continues to see companies showcasing promising therapeutics for multiple disease indications. As the conference enters its fourth day, BioSpace takes a look at a few of the presentations.

Capsida Biotherapeutics

California-based Capsida showcased its therapeutic approach that the company believes will unlock the potential to treat both rare and common diseases across all ages.

Capsida shared its early generation AAV-engineered pilot programs, as well as results from its capsid engineering platform used to select adeno-associated virus 9 (AAV9)-based vectors for the treatment of diseases of the central nervous system. In its presentation, Capsida Chief Executive Officer Peter Anastasiou said the data demonstrate improved distribution throughout the cortical, subcortical, and deep brain regions at low doses via IV administration compared to invasive AAV9 dosing methods.

The company also included an oral presentation dubbed CAP-001: Systemic AAV Gene Therapy With Next-Generation Capsids for MPS II Disease. CAP-001 is a novel engineered capsid packaging a human iduronate-2-sulfatase (IDS) transgene. The company noted CAP-001 was selected for further characterization as a proof of concept to treat mucopolysaccharidosis type II (MPS II), or Hunter Syndrome, a lysosomal storage disorder.

When administered intravenously, results showed that CAP-001 achieved better biodistribution across the brain than AAV9 through other administered routes. It also provided a significantly more uniform distribution across all brain areas witha >50-fold improvement in subcortical and deep-brain regions, an area where ICM delivery has proven to poorly distribute.

Instill Bio

Texas-based Instil Bio showed off results of genomic and correlative analyses in a cohort of patients with metastatic melanoma treated with tumor-infiltrating lymphocytes (TIL). In its presentation this week, Instil showed a correlation between tumor response and clonal expansion of TILs.

Additionally, the company noted in its oral abstract that there is an inverse correlation between tumor response and specific T cell populations. Instil said that expression profiling and transcriptional network analysis points to what it called master regulator genes that can be manipulated during TIL manufacturing to enhance TIL activity.

We believe that TILs represent more than a potential therapy for patients, as they are also a platform to understand fundamental T cell biology, Bronson Crouch, chief executive officer of Instil Bio said in a statement. We are applying the recent advances in analytical technologies to deeply probe the function of TILs, and expect to generate insights that could be foundational for the development of anti-cancer therapies.

Adverum Biotechnologies

California-based Adverum presented data that further supports its Phase-II development plans for ADVM-022, a therapeutic candidate for wet age-related macular degeneration (wet AMD). Data presented shows results from non-human primate studies that support the companys planned 6 X 10^10 vg/eye (6E10) dose expected to be used in its next clinical trial.

Data highlights from the presentation show that the human equivalent dose of 6E10 (3 X 10^10 vg/eye dose in NHP) demonstrated potential therapeutic levels in both aqueous humor and vitreous humor, the company said. Also, Adverum said the administration of the human equivalent dose of 6E10 (3 X 10^10 vg/eye dose in NHP) was well tolerated. No adverse clinical signs were observed during the three-month study, the company added.

We are highly encouraged by the aflibercept expression levels and tolerability of the human equivalent dose of 6x10^10 vg/eye supported by our data in non-human primates, Richard Beckman, chief medical officer of Adverum Biotechnologies said in a statement. As we explore doses of 2x10^11 vg/eye and lower, we are excited by the potential of enhancing the safety profile while building on the robust response that ADVM-022 has demonstrated to date in wet AMD.

Metagenomi

Bay Area-based Metagenomi presented preclinical data on novel gene-editing systems that have shown extremely high editing efficiency in human primary immune cells and the ability to integrate at multiple, targeted sites. At ASGCT, the company made two presentations.

The first study, CRISPR-Associated Gene-Editing Systems Discovered in Metagenomic Samples Enable Efficient Genome Engineering in Multiple Primary Immune Cell Types, showcased Metagenomis CRISPR-associated gene editing systems ability to edit primary human cells with high efficiency, including T cells, natural killer cells, B cells, hematopoietic stem cells and induced pluripotent stem cells. The company said they reached an editing efficiency of more than 95%.

The second presentation, Active CRISPR-Associated Transposases from Natural Environments, showed off a novel family of proprietary CRISPR-associated transposase (CAST) gene-editing systems. CASTs

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Capsida, Adverum, Instil and Metagenomi Showcase Therapies at ASGCT - BioSpace

PARIS--(BUSINESS WIRE)-- Regulatory News:

GenSight Biologics (Euronext: SIGHT, ISIN: FR0013183985, PEA-PME eligible), a biopharma Company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders, today announced that the highly-regarded Journal of Neuro-Ophthalmology has published a qualitative study to explore the impact of Leber Hereditary Optic Neuropathy (LHON) on patients and their relatives. The study was featured in a paper published on the journals website last month titled, The Impact of Leber Hereditary Optic Neuropathy on the Quality of Life of Patients and Their Relatives: A Qualitative Study. It is the first of its kind to explore this condition and its impact for patients and relatives in four different countries.

The study determined that the impact of LHON extends beyond vision-related activity limitations, while addressing its psychosocial impact. It concluded that helping patients and their relatives adapt and cope with vision loss is vital. An accurate and timely diagnosis for patients is also crucial to address these issues and also to allow for early intervention.

This study is the first to describe the impact of LHON on the families of affected individuals. Partners and families of affected individuals take on many responsibilities and shoulder some of the burden of LHON. The impact that LHON has on partners and families has not been reported previously and it is vital that we acknowledge the support and care that they provide, explained Patrick Yu-Wai-Man, MD, PhD, Moorfields Eye Hospital and Department of Clinical Neurosciences, University of Cambridge, United Kingdom.

Participants reported feeling devastated by the diagnosis of LHON after a lengthy and worrisome diagnostic journey. They were also frustrated by the loss of autonomy that affected their relatives. Participants described challenges across several domains: physical capabilities, emotional well-being, interpersonal relationships, work and studies, finances, and recreational activities.

Additionally, the study determined that despite residing in different countries, LHON patients and their relatives described similar experiences in the four areas of focus in this study. These areas include (1) experience leading to the point of diagnosis; (2) impact of their condition on various aspects of life; (3) perceptions about treatment; and (4) expectations toward future therapies.

This study confirms what we have known all along in the eye clinic - that LHON impacts every aspect of quality of life, not just activities that rely on vision. Understanding how LHON affects individuals who develop vision loss enables doctors to intervene early and provide care that will improve the quality of life of affected individuals, commented Benson Chen, MD, Department of Clinical Neurosciences, University of Cambridge, United Kingdom. This might include different kinds of assessments in the eye clinic that measure the emotional and psychological impact of LHON or developing the referral pathways that enable affected individuals to access psychological support and work or skills re-training, he added.

LHON is an inherited mitochondrial disease characterized by severe bilateral vision loss and chronic visual impairment. The objective of this study was to comprehensively explore the impact of LHON on the lives of patients and their relatives at the time of diagnosis and now.

The qualitative study design encompassed eight focus group interviews conducted in France, Germany, the United Kingdom, and the United States, involving 17 individuals with m.11778G>A mutation and their relatives. Separate focus groups for patients and their relatives were facilitated by a moderator in French, German, or English. Neuro-ophthalmologists in the four countries who participated helped to identify additional patients who fulfilled under-represented sampling criteria. The four countries were selected because all have established networks of individuals with LHON and were places where previous LHON studies have been conducted.

Focus group interviews were conducted as part of a market research study sponsored by GenSight Biologics, and independently designed and conducted by groupH, a health care market research and analytics firm. The design and conduct of the study complied with the European Pharmaceutical Market Research Association and British Healthcare Business Intelligence Association guidelines.

We, at GenSight, have long been convinced that by providing an innovative therapeutic solution for LHON we would offer much more than an improved vision. Documenting the impact of LHON experienced by all study participants highlights the fact that we could empower patients and improve their ability to enjoy a fulfilling life, while easing the demands on their loved ones. This is precisely why we are dedicated to developing a long-lasting therapeutic solution for patients with LHON, explained Magali Taiel, Chief Medical Officer of GenSight. We are hopeful that we may one day help patients to recover not only their vision, but also their sense of autonomy and well-being, she added.

Full text versions of this article are available on the journals website: https://journals.lww.com/jneuro-ophthalmology/Abstract/9900/The_Impact_of_Leber_Hereditary_Optic_Neuropathy_on.77.aspx.

*About the paper:

The Impact of Leber Hereditary Optic Neuropathy on the Quality of Life of Patients and Their Relatives: A Qualitative Study

Authors: Benson S. Chen, MD, Erik Holzinger, MBA, Magali Taiel, MD, Patrick Yu-Wai-Man, MD, PhD

References: 1. Carelli V, Carbonelli M, de Coo IF, Kawasaki A, Klopstock T, Lagrze WA, La Morgia C, Newman NJ, Orssaud C, Pott JWR, Sadun AA, van Everdingen J, Vignal-Clermont C, Votruba M, Yu- Wai-Man P, Barboni P. International consensus statement on the clinical and therapeutic management of Leber hereditary optic neuropathy. J Neuroophthalmol. 2017;37:371381.2. Wallace DC, Singh G, Lott MT, Hodge JA, Schurr TG, Lezza AM, Elsas LJ II, Nikoskelainen EK. Mitochondrial DNA mutation associated with Lebers hereditary optic neuropathy. Science. 1988;242:14271430.3. Newman NJ, Carelli V, Taiel M, Yu-Wai-Man P. Visual outcomes in Leber hereditary optic neuropathy patients with the m.11778G.A (MTND4) mitochondrial DNA mutation. J Neuroophthalmol. 2020;40:547557.4. Yu-Wai-Man P, Newman NJ, Carelli V, La Morgia C, Biousse V, Bandello FM, Clermont CV, Campillo LC, Leruez S, Moster ML, Cestari DM, Foroozan R, Sadun A, Karanjia R, Jurkute N, Blouin L, Taiel M, Sahel JA; Group LRS. Natural history of patients with Leber hereditary optic neuropathy-results from the REALITY study. Eye (Lond). 2021 Apr 28 doi: https://doi.org/10.1038/ s41433-021-01535-9 (epub ahead of print).5. Braithwaite T, Calvert M, Gray A, Pesudovs K, Denniston AK. The use of patient-reported outcome research in modern ophthalmology: impact on clinical trials and routine clinical practice. Patient Relat Outcome Meas. 2019;10:924.6. Mangione CM, Lee PP, Gutierrez PR, Spritzer K, Berry S, Hays RD. National Eye Institute visual function questionnaire field test I. Development of the 25-item National Eye Institute visual function questionnaire. Arch Ophthalmol. 2001;119:10501058.7. Kirkman MA, Korsten A, Leonhardt M, Dimitriadis K, De Coo IF, Klopstock T, Griffiths PG, Hudson G, Chinnery PF, Yu-Wai-Man P. Quality of life in patients with Leber hereditary optic neuropathy. Invest Ophthalmol Vis Sci. 2009;50:31123115.8. Cui S, Jiang H, Peng J, Wang J, Zhang X. Evaluation of vision- related quality of life in Chinese patients with Leber hereditary optic neuropathy and the G11778A mutation. J Neuroophthalmol. 2019;39:5659.9. Gale J, Khoshnevis M, Frousiakis SE, Karanjia R, Poincenot L, Sadun AA, Baron DA. An international study of emotional response to bilateral vision loss using a novel graphical online assessment tool. Psychosomatics. 2017;58:3845.10. Garcia GA, Khoshnevis M, Gale J, Frousiakis SE, Hwang TJ, Poincenot L, Karanjia R, Baron D, Sadun AA. Profound vision loss impairs psychological well-being in young and middle-aged individuals. Clin Ophthalmol. 2017;11:417427.11. Gale NK, Heath G, Cameron E, Rashid S, Redwood S. Using the framework method for the analysis of qualitative data in multi- disciplinary health research. BMC Med Res Methodol. 2013;13:117.12. Steinberg EP, Tielsch JM, Schein OD, Javitt JC, Sharkey P, Cassard SD, Legro MW, Diener-West M, Bass EB, Damiano AM, Steinwachs DM, Sommer A. The VF-14. An index of functional impairment in patients with cataract. Arch Ophthalmol. 1994;112:630638.13. Cohen JS, Biesecker BB. Quality of life in rare genetic conditions: a systematic review of the literature. Am J Med Genet A. 2010;152A:11361156.14. von der Lippe C, Diesen PS, Feragen KB. Living with a rare disorder: a systematic review of the qualitative literature. Mol Genet Genomic Med. 2017;5:758773.15. James CA, Hadley DW, Holtzman NA, Winkelstein JA. How does the mode of inheritance of a genetic condition influence families? A study of guilt, blame, stigma, and understanding of inheritance and reproductive risks in families with X-linked and autosomal recessive diseases. Genet Med. 2006;8:234242.16. Turriff A, Nolen R, DAmanda C, Biesecker B, Cukras C, Sieving PA. There are hills and valleys: experiences of parenting a son with X-linked retinoschisis. Am J Ophthalmol. 2020;212:98104.17. Nyumba TO, Wilson K, Derrick CJ, Mukherjee N. The use of focus group discussion methodology: insights from two decades of application in conservation. Methods Ecol Evol. 2018;9:2032.

About GenSight Biologics

GenSight Biologics S.A. is a clinical-stage biopharma company focused on developing and commercializing innovative gene therapies for retinal neurodegenerative diseases and central nervous system disorders. GenSight Biologics pipeline leverages two core technology platforms, the Mitochondrial Targeting Sequence (MTS) and optogenetics, to help preserve or restore vision in patients suffering from blinding retinal diseases. GenSight Biologics lead product candidate, LUMEVOQ (GS010; lenadogene nolparvovec), has been submitted for marketing approval in Europe for the treatment of Leber Hereditary Optic Neuropathy (LHON), a rare mitochondrial disease affecting primarily teens and young adults that leads to irreversible blindness. Using its gene therapy-based approach, GenSight Biologics product candidates are designed to be administered in a single treatment to each eye by intravitreal injection to offer patients a sustainable functional visual recovery.

About Leber Hereditary Optic Neuropathy (LHON)

Leber Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial genetic disease, characterized by the degeneration of retinal ganglion cells that results in brutal and irreversible vision loss that can lead to legal blindness, and mainly affects adolescents and young adults. LHON is associated with painless, sudden loss of central vision in the 1st eye, with the 2nd eye sequentially impaired. It is a symmetric disease with poor functional visual recovery. 97% of patients have bilateral involvement at less than one year of onset of vision loss, and in 25% of cases, vision loss occurs in both eyes simultaneously. The estimated incidence of LHON is approximately 800-1,200 new patients who lose their sight every year in the United States and the European Union.

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Source: GenSight Biologics S.A.

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GenSight Biologics Announces Publication of a Study of the Impact of LHON Disease on the Lives of Patients and Relatives in Journal of...

Published on May 19, 2022

Hypertension or increased blood pressure may occur in Diabetics because of the impact of Diabetes on the walls of the arteries and the fluid balance. Hypertension may however co-exist as an independent risk factor along with Diabetes Mellitus. In either case, it can significantly increase the chances of developing heart conditions or conditions like stroke as well as the risk of developing other complications like renal or eye related conditions like nephropathy, retinopathy etc.

Consensus guidelines from the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, the American Diabetes Association (ADA) and the National Kidney Foundation (NKF) recommend a blood pressure goal of less than 130/80 mm Hg in patients with diabetes. Based on the recent survey report conducted by Indus Health Plus, it was found that 26% of the people tested had high blood pressure out of which 13% had systolic blood pressure above 140 mm Hg. The sample size of the report was 21000. Controlling hypertension is the key to reducing cardiovascular risk in patients with diabetes. It is an integral component of a comprehensive care plan that should include optimal management of diabetes and hyperlipidaemia, aspirin therapy, and lifestyle modifications.

How can Diabetes cause hypertension?

In diabetes, the body does not produce enough insulin so it does not work effectively, or they cannot process glucose. Insulin is a hormone that aids the body in converting glucose from food into energy. When a person has insulin issues, glucose cannot enter their cells to provide energy, so it accumulates in the bloodstream instead. In addition to causing widespread damage to tissues and organs, high blood glucose can also interfere with the control of blood pressure. Damage to the blood vessels and kidneys can increase blood pressure, for instance.

How can you prevent or control both Diabetes and Hypertension effectively?

Lifestyle modifications include following appropriate diet, engaging in 30 to 45 minutes of moderate-intensity activity most days of the week, avoiding smoking and alcohol. Appropriate medical treatment needs to be followed with good compliance for controlling the two conditions effectively. Here are some preventive measures that people can take to control these conditions in an effective manner.

Diabetes and hypertension often occur together and have multiple risk factors and causes in common. The risk of developing one condition increases when a person has another. The early detection and treatment of hypertension and diabetes can prevent serious complications. A healthy lifestyle can help manage blood pressure and blood glucose levels.

The article is contributed by Mr. Amol Naikawadi, Joint Managing Director and Preventive Healthcare Specialist, Indus Health Plus

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How Diabetes can be a driver for High blood pressure and eventually leads to Hypertension - APN News

Akouos, Inc.

- Nonclinical data demonstrate that a single intracochlear administration of an AAVAnc80 vector led to durable restoration of auditory function and was well tolerated, supporting planned clinical development of AK-OTOF for the treatment of OTOF-mediated hearing loss

- MicroRNA target site (miR-TS)-incorporation in AAV vectors is shown to have potential benefits for de-targeting transgene expression in the inner ear, supporting future development of gene therapies targeting a broad range of inner ear conditions

BOSTON, May 19, 2022 (GLOBE NEWSWIRE) -- Akouos, Inc. (NASDAQ: AKUS), a precision genetic medicine company dedicated to developing potential gene therapies for individuals living with disabling hearing loss worldwide, presented nonclinical data at the American Society of Gene and Cell Therapy (ASGCT) 25th Annual Meeting. The company gave two nonclinical presentations at the meeting: one that supports the planned clinical development of AK-OTOF, a gene therapy intended for the treatment of OTOF-mediated hearing loss; and another that supports the potential use of microRNA target site (miR-TS) in adeno-associated viral (AAV) vectors for regulated gene expression in the inner ear.

We are excited to present these nonclinical data, which highlight our precision genetic medicine platform and the potential of genetic medicines to address a broad range of inner ear conditions, to the gene and cell therapy community. The AK-OTOF nonclinical data demonstrate durable restoration of auditory function and show that the product candidate was systemically and locally well tolerated in two translationally relevant animal species, said Manny Simons, Ph.D., founder, president, and chief executive officer of Akouos. As we continue to progress toward planned IND submissions for AK-OTOF in the first half of 2022 and AK-antiVEGF in 2022, we are encouraged by the growing body of evidence supporting these filings, as well as by our efforts to advance preclinical development of other potential gene therapies for inner ear conditions, such as GJB2-mediated hearing loss, and to develop platform capabilities that can be applied to regenerative medicine approaches in the inner ear.

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Nonclinical In Vivo Expression, Durability of Effect, Biodistribution/Shedding, and Safety Evaluations Support Clinical Development of AK-OTOF (AAVAnc80-hOTOF Vector) for OTOF-mediated Hearing Loss Presenting Author: Ann E. Hickox, Ph.D.Session Title and Room: Ophthalmic and Auditory Diseases; Salon G

AK-OTOF is an AAV vector-based gene therapy intended for the treatment of patients with otoferlin gene (OTOF)-mediated hearing loss by delivering transgenes encoding OTOF to inner hair cells (IHCs). Following intracochlear delivery, and subsequent co-transduction of IHCs by each component vector, the two transgene products recombine to generate a full-length otoferlin mRNA transcript and subsequently a full-length otoferlin protein. Results from this presentation show:

Intracochlearadministration of AK-OTOF in otoferlin knockout (Otof-/-) mice, or its tagged version (AAVAnc80-FLAG.hOTOF) in non-human primates (NHPs), leads to full-length human otoferlin protein expression only in the target IHCs;human otoferlin expression in IHCs ofOfof-/-mice restores auditory functionas early as two weeks post-administration and restoration was durable through at least six months.

AK-OTOF was systemically and locally well tolerated in both mice and NHPs, and no adverse effects were observed inclinical pathology,oticpathology, systemic histopathology, or auditoryor cochlearfunction.

Limited systemic exposure of AK-OTOF following intracochlear administration was observed,and no otoferlin protein expression was detected in any non-target tissue types evaluated, including those with detectable levels of vector sequences and otoferlin mRNAexpression.

Together, these nonclinical studies further support the planned clinical development of AK-OTOF for the treatment of OTOF-mediated hearing loss.

The digital presentation is located at https://akouos.com/gene-therapy-resources/.

Evaluating miR-Target Sites as a Strategy to Allow AAV Vector-based De-targeting of Gene Expression in the Inner EarPresenting Author: Richard M. Churchill Jr.Poster Board Number: Tu-37

In the development of AAV gene therapy vectors, a goal is to generate safe and effective product candidates that deliver targeted transgene expression. Ubiquitous promoters can drive strong widespread expression in the inner ear in mice and NHPs. This expression can be well tolerated across the inner ear, as is the case for Akouoss first two programs, AK-OTOF and AK-antiVEGF. Addition of selective cis-regulatory elements may be needed for sometransgenes, such asGJB2,where expressionin a portion of nontarget cells is not welltolerated. This nonclinical study explored the potential use of miR-TS incorporation in AAV vectors for de-targeting transgene expression in different cell types of the cochlea. Using an in vitro model, expression of transgene mRNA and protein in the presence or absence of the target sites was evaluated. Akouosidentified multiplemicroRNA target sitesto drivevarious differential expression patterns demonstrating that a combination of AAVAnc80 andmiR-TScan driveexpression in supportingcells, while limiting expression in hair cells incochlear explants. Future work will focus on evaluating miR-TS regulation in vivo and identifying combinations of different miR-TSs to enhance de-targeting in specific cell types where, for example, expression driven by ubiquitous promoters is not well tolerated.

The digital presentation is located at https://akouos.com/gene-therapy-resources/.

About AkouosAkouos is a precision genetic medicine company dedicated to developing gene therapies with the potential to restore, improve, and preserve high-acuity physiologic hearing for individuals living with disabling hearing loss worldwide. Leveraging its precision genetic medicine platform that incorporates a proprietary adeno-associated viral (AAV) vector library and a novel delivery approach, Akouos is focused on developing precision therapies for forms of sensorineural hearing loss. Headquartered in Boston, Akouos was founded in 2016 by leaders in the fields of neurotology, genetics, inner ear drug delivery, and AAV gene therapy.

Forward-Looking StatementsStatements in this press release about future expectations, plans and prospects, as well as any other statements regarding matters that are not historical facts, may constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to the initiation, plans, and timing of our future clinical trials and our research and development programs, and the timing of our IND submissions for AK-OTOF and AK-antiVEGF. The words anticipate, believe, continue, could, estimate, expect, intend, may, plan, potential, predict, project, should, target, will, would, and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: our limited operating history; uncertainties inherent in the development of product candidates, including the initiation and completion of nonclinical studies and clinical trials; whether results from nonclinical studies will be predictive of results or success of clinical trials; the timing of and our ability to submit applications for, and obtain and maintain regulatory approvals for, our product candidates; our expectations regarding our regulatory strategy; our ability to fund our operating expenses and capital expenditure requirements with our cash, cash equivalents, and marketable securities; the potential advantages of our product candidates; the rate and degree of market acceptance and clinical utility of our product candidates; our estimates regarding the potential addressable patient population for our product candidates; our commercialization, marketing, and manufacturing capabilities and strategy; our ability to obtain and maintain intellectual property protection for our product candidates; our ability to identify additional products, product candidates, or technologies with significant commercial potential that are consistent with our commercial objectives; the impact of government laws and regulations and any changes in such laws and regulations; risks related to competitive programs; the potential that our internal manufacturing capabilities and/or external manufacturing supply may experience delays; the impact of the COVID-19 pandemic on our business, results of operations, and financial condition; our ability to maintain and establish collaborations or obtain additional funding; and other factors discussed in the Risk Factors section of our Quarterly Report on Form 10-Q for the quarter ended March 31, 2022, which is on file with the Securities and Exchange Commission, and in other filings that Akouos may make with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and the Company expressly disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.

Contacts

Media:Katie Engleman, 1ABkatie@1abmedia.com

Investors:Courtney Turiano, Stern Investor Relations Courtney.Turiano@sternir.com

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Akouos Presents Nonclinical Data Supporting the Planned Clinical Development of AK-OTOF and Strategies for Regulated Gene Expression in the Inner Ear...

Investors are seeking out biotech companies that create unique technologies to solve problems. Recent money on the move saw funding support for a platform that selectively degrades DNA, software to help read mammograms and a company using corn genetics to develop cancer-targeting viruses.

SwanBio Therapeutics

Founding investors Syncona Limited and Mass General Brigham Ventures led a Series B financing round for SwanBio Therapeutics. Together, they raised $56 million, bringing SwanBios total funds raised to $133 million.

The new money will support the company as it evolves into a fully integrated research and development organization. A main priority is the clinical advancement of SBT101, the first clinical-stage AAV-based gene therapy candidate for the treatment of adrenomyeloneuropathy. The drug received a Fast Track designation and an Orphan Drug designation, and the U.S. Food and Drug Administration cleared an Investigational New Drug Application for the drug earlier in 2022.

In addition to SBT101, the funding will help develop other therapies for monogenic and polygenic disorders.

Locus Biosciences

North Carolina-based Locus Biosciences announced a $35 million financing, which included a Series B equity financing as well as the conversion of an earlier convertible note. The funding included investors such as Artis Ventures, Viking Global Investors, Discovery Innovations and Johnson and Johnson Innovation JJDC, Inc.

The funding will support Locus lead candidate LBP-EC01, a crPhage precision medicine targeting Escherichia coli (E. coli) bacteria. The company plans to advance the drug into a registrational Phase II/III trial. The funding will also support in-house manufacturing capabilities and the expansion of Locuss discovery platform engine.

Remix Therapeutics

A $70 million Series B financing will help Cambridge, Massachusetts-based Remix Therapeutics hone its proprietary technology platform. The platform uses data analytics to identify and reprogram RNA processing to enhance protein function, eliminate protein function or correct dysregulation in order to treat genetic diseases. Remix is collaborating with Janssen Pharmaceutica NV, part of Johnson & Johnsons Janssen Pharmaceutical Companies, to develop small-molecule therapeutics that modulate RNA processing.

The funding was led by existing investors such as Foresite Capital, Arch Venture Partners, Casdin Capital and Atlas Venture, as well as a new investor, Surveyor.

"This financing will support further development of our REMaster platform, which enables the design of molecules that can selectively degrade RNA, enhance RNA expression, induce exon skipping, or rescue genetic lesions, said Peter Smith, Ph.D., co-founder and CEO of Remix. This technology will transform how diseases are treated."

Mirvie

San Francisco-based Mirvie raised $60 million in a Series B round of funding, bringing its financing to a total of $90 million. The funding, led by Decheng Capital, included many venture capital firms, as well as a new investor: Allyson Felix, a seven-time Olympic gold medalist and maternal health advocate. Felix and her daughter survived severe preeclampsia, and now Felix is supporting Mirvies mission of understanding the underlying biology of each pregnancy to improve maternal health. The funding from the Series B will help Mirvie continue developing its RNA platform, which can predict preeclampsia months before patients experience life-threatening complications.

Vyriad, Inc.

In a Series B round of funding, Minnesota-based Vyriad pulled in $29.5 million. This brings the companys total raised funds to over $100 million, thanks to existing investors such as Mayo Clinic, Regeneron Pharmaceuticals and the Southeast Minnesota Capital Fund, as well as new investors such as Mr. Harry Stine of Stine Seed Farms. Stine Seed Farms develops corn and soybean seeds through genetic breeding programs.

I was amazed to learn that Vyriad's approach for developing safe, effective, cancer-targeted oncolytic viruses closely mirrors the Stine Seed model of high throughput screening, selection and commercialization of novel soybean and corn strains," said Dr. Stephen Russell, co-founder and CEO of Vyriad.

Privately held Vyriad will use the funds to advance its pipeline of oncolytic viruses that can be used, either alone or in combination with other therapies, to fight cancer, using the high-throughput genetics model that Stine used to develop agricultural germplasms.

Cynosure

Cynosures lead investor, Clayton, Dubilier & Rice, pledged $60 million in funding to help the company continue innovating and bringing medical aesthetics technologies to market. Cynosure has seen explosive growth recently, with sales growing over 45% in 2021 and over 30% year-over-year in the first quarter of 2022.

"Medical aesthetics is a large market with strong macro tailwinds that have only gotten stronger across the globe since our initial investment," said Derek Strum, a partner at Clayton, Dubilier & Rice. "We believe Cynosure is well-positioned to build on its momentum and capture both organic and inorganic growth opportunities."

Genascence

After a seed round of financing in 2019, clinical-stage biotech company Genascence closed a $10.5 million Series A financing. Pacira BioSciences, a leading non-opioid pain management company, led the funding with support from Polymerase Capital, the University of Florida Research Foundation and DeepWork Capital. The goal of the funding is to advance the companys gene therapies for musculoskeletal diseases. One of the priorities is to advance GNSC-001, the company's lead program in osteoarthritis. GNSC-001 is a genetic medicine called a recombinant adeno-associated vector and it has an inhibitor of interleukin-1, a key mediator in the pathogenesis of osteoarthritis.

Tubulis

Germany-based Tubulis completed a Series B financing worth 60 million (USD $63 million). The funding, led by Andera Partners, also involved new investors Evotec and Fund+. Tubulis develops antibody-drug conjugates (ADCs), and with the funding, the company hopes to advance its proprietary pipeline of ADCs towards clinical evaluation. Tubulis also plans to introduce programs addressing a range of solid tumor indications.

This funding emphasizes that Tubulis is uniquely positioned to consolidate the findings of the last 20 years in the ADC field and translate this understanding into meaningful therapeutic benefits for patients, said Dominik Schumacher, Ph.D., CEO and co-founder of Tubulis.

OMass Therapeutics

Several new investors joined OMass Therapeutics Series B financing to raise $100 million in total. Investors such as Sanofi Ventures, Northpond Ventures and GV joined veteran backers Oxford Science Enterprises, Oxford University and Syncona to gather funding for OMasss portfolio of highly validated target ecosystem medicines for membrane- and complex-bound proteins. Specifically, the funding will help the company develop an antagonist of the MC2 receptor to help treat congenital adrenal hyperplasia.

Curebase

San Francisco-based Curebase gathered $40 million in a Series B round of funding. Industry Ventures led the round, along with existing investors GGV Capital, Bold Capital and Xfund and new investors such as Acrew Capital, Positive Sum and World Innovation Lab. The round also included an investment from Gilead Sciences.

Since 2017, Curebase has raised $59 million to achieve its mission of democratizing access to clinical studies. The Series B funding will specifically go toward developing an end-to-end clinical trial execution model, furthering its eClinical software platform, honing its virtual and hybrid site capacities and enriching its capabilities for interventional drug sponsors and global studies.

InxMed

China-based InxMed completed a $15 million Series B+ financing. Funded by Hyfinity Investments, the financing will help the company accelerate clinical trials in China and the United States of its highly selective adenosine triphosphate competitive FAK inhibitor called IN10018.

IN10018 received a Fast Track Designation from the FDA in August 2021. With the Series B+ funds, InxMed will actively explore global partnership opportunities to accelerate more value inflections of IN10018 and other programs.

Aspen Neuroscience

Private autologous cell therapy company Aspen Neuroscience closed a Series B funding worth $147.5 million. GV, LYFE Capital and Revelation Partners co-led the round, along with support from new investors as well as some Series A and seed funding teams. Together, they have now raised more than $220 million for Aspen.

The goal of the funding is to support a patient Screening Cohort study and a Phase I/II post-IND submission study for ANPD001, which is designed to help treat Parkinsons disease.

Domain Therapeutics

Domain Therapeutics closed a $42 million Series A financing. Co-led by Panacea Venture, CTI Life Sciences and 3B Future Health Fund, the round also included several new investors and one existing investor, Seventure Partners.

Domain is a biopharmaceutical company developing new drug candidates targeting G Protein-Coupled Receptors (GPCRs), a class of drug targets. The funding will support the company as it clinically develops its EP4R antagonist, DT-9081, as well as advances two other CPCR programs and progresses its pipeline for first-in-class assets targeting GPCRs.

Invetx

In an oversubscribed Series B round of financing, Invetx raised $60.5 million. F-Prime Capital, Novo Holdings, GV and Eight Roads co-led the round with support from existing investors such as Anterra Capital and Casdin Capital.

Invetx, which develops protein-based therapeutics for animal health, will use the funds to advance its pipeline of monoclonal antibody products for chronic and serious diseases in dogs and cats.

With the support of several top-tier investors in this latest financing, Invetx is well-capitalized to continue advancing its novel veterinary products towards approval and commercialization, said Invetx CEO Juergen Horn, PhD.

Therapixel

When Therapixel closed its Series B financing, it had raised 15 M (USD$15.76 million). The funding was led by Crdit Mutuel Innovation and CapHorn along with support from existing investors such as Omnes, IT-Translation, M-Capital and Rgion Sud Investissement. With the investors financial backing, Therapixel will expand its presence in the U.S. and launch more features for its MammoScreen AI software for reading mammography.

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Money on the Move: SwanBio, Remix, Locus, Mirvie and More - BioSpace

DiNAQOR DiNAMIQS offers comprehensive range of biomanufacturing services,GMP-compatible process development, quality control and analytical development

ZURICH-SCHLIEREN, Switzerland, May 16, 2022 /PRNewswire/ --DiNAQOR announced today the launch of DiNAQOR DiNAMIQS, a biomanufacturing subsidiary, that will accelerate development timelines and reduce costs and risk for genetic medicine companies bringing new treatments to market.

DiNAQOR DiNAMIQS is based in the company's state-of-the-art, 1,200-square-meter (13,000 square feet) manufacturing facility in Bio-Technopark Schlieren-Zrich, the leading center for biotechnology companies in Central Europe. DiNAQOR's Chief Technology Officer, Eduard Ayuso, will serve as the CEO of DiNAQOR DiNAMIQS.

"We look forward to partnering with the world's leading gene therapy companies," said Johannes Holzmeister, M.D., Chairman and CEO of DiNAQOR."There are always challenges in the development process, and DiNAQOR DiNAMIQS is ideally suited to meet and overcome them. Manufacturing viral vectors at meaningful bioreactor scale and using GMP-compatible processes for preclinical studies will improve quality and safety while accelerating development timelines for genetic medicines."

DiNAQOR DiNAMIQS provides a comprehensive range of manufacturing services, process development, quality control and analytics solutions to support and accelerate gene therapy projects.

The DiNAMIQS platform employs innovative upstream and downstream processes and provides high-quality recombinant adeno-associated viral (AAV) vector manufacturing suitable for both in vitro and in vivo R&D applications up to 50L scale. Aligned with GMP regulations, the manufacturing protocol provides researchers with high quality vectors and minimal changes as projects progress toward clinical applications. DiNAMIQS is currently building a state-of-the-art GMP-compliant 2,400-square-meter (26,000 square feet) facility that can produce viral vectors at 500L scale.

DiNAQOR DiNAMIQS is also pioneering customizable, GMP-compatible process development that accelerates research and development efforts and is guided by a diagnostic procedure to determine relevant bioprocessing solutions. DiNAMIQS' process development expertise includes biomass expansion in bioreactor, large-scale transfection, harvest and clarification, ultrafiltration/diafiltration, affinity chromatography capture, ion exchange chromatography, preparative ultracentrifugation, desalting, dynamic dialysis, formulation, sterile filtration, automation assisted fill and finish.

Genetic medicinecompanies partnering with DiNAQOR DiNAMIQS will also use analytics that yield critical insights on viral vector potency, identity, and purity. DiNAMIQS in-house capabilities include digital PCR-based methods for titer quantification, ELISA, purity analyses, TCID50 infectivity assays and testing for bacterial endotoxins.

"Our state-of-the-art facility and stellar viral vector manufacturing team are prepared to help gene therapy developers bring their therapies efficiently to the clinic. I intend to bring my learnings from 20 years' experience in the field to our partners and provide them with high quality vectors. DiNAMIQS will shorten the time to market by closing the gaps between research grade vector supply, process development and GMP manufacturing," said Eduard Ayuso, CEO of DiNAQOR DiNAMIQS.

"Additionally, many promising gene therapy programs slow down when the costs associated with scaling up their manufacturing begin to mount. Our biomanufacturing expertise will enable these projects to move forward in a cost-effective way -- and do so quickly."

To learn more about DiNAQOR DiNAMIQS, visit http://www.dinamiqs.com.

About DiNAQORDiNAQOR is a life sciences platform company that is pioneering proprietary human-based tissue drug development and technology to enable organ-specific delivery of gene therapies and other therapeutics. The company is headquartered in Zurich-Schlieren, Switzerland, with additional presence in London, England; Hamburg, Germany; and Laguna Hills, California. For more information visit http://www.dinaqor.com.

Contact:KWM CommunicationsKellie Walsh914-315-6072[emailprotected]

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DiNAQOR Opens DiNAMIQS Subsidiary to Partner with Gene Therapy Companies Bringing New Treatments to Patients - PR Newswire

LEXINGTON, Mass., May 17, 2022 /PRNewswire/ -- LogicBio Therapeutics, Inc.(Nasdaq: LOGC), a clinical-stage genetic medicine company, today announced that president and chief executive officer,Frederic Chereau, will present a company overview at the H.C. Wainwright Global Investment Conferencebeing heldMay 23-26, 2022. The pre-recorded presentation will be available for on-demand viewing beginning at7:00 a.m. ETonTuesday, May 24, 2022.

A webcast of the presentation will be made available on the Investors section of the company's website athttps://investor.logicbio.com/. The webcast replay will be available for approximately 30 days.

AboutLogicBio Therapeutics

LogicBio Therapeuticsis a clinical-stage genetic medicine company pioneering genome editing and gene delivery platforms to address rare and serious diseases from infancy through adulthood. The company's genome editing platform, GeneRide, is a new approach to precise gene insertion harnessing a cell's natural DNA repair process potentially leading to durable therapeutic protein expression levels. The company's gene delivery platform, sAAVy, is an adeno-associated virus (AAV) capsid engineering platform designed to optimize gene delivery for treatments in a broad range of indications and tissues. The company's proprietary system, mAAVRx, aims to overcome some of the current limitations of AAV manufacturing by optimizing the transfection process to improve yields and product quality. The company is based inLexington, MA.For more information, visitwww.logicbio.com, which does not form a part of this release.

Investor Contacts: Stephen Jasper Gilmartin Group 858-525-2047 [emailprotected]

Media Contacts: Adam Daley Berry & Company Public Relations W:212-253-8881 C: 614-580-2048 [emailprotected]

SOURCE LogicBio Therapeutics, Inc.

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LogicBio Therapeutics to Present at HC Wainwright Global Investment Conference - PR Newswire

Sequencing the genome of cancer tumours is often used to help identify the type of cancer a person has and the best treatment for it.

Although cancer genomics has been used for a few years now, scientists are still learning about the best way to use genomic information to grade and categorize cancers.

One area that has received little attention until now is the methylation status of the cancer genome around specific genes. Methylation refers to the presence or absence of a methyl group on a base molecule within a gene that can affect whether or not a gene is expressed. This control of genetic expression is referred to as epigenetics.

Levels of expression of certain genes can also be affected by copy number variants (CNVs). CNVs arise because some sections of DNA are repeated, and the number of repeats varies between individuals due to deletions or duplications of DNA.

This leaves some people with many copies of a particular DNA sequence, whilst others have far fewer. These variations between individuals can be normal and harmless however, they can also underpin disease.

A type of brain cancer called meningioma is known for the diversity of CNVs that occur between the genomes of different tumors. CNVs can also affect methylation, which further affects gene expression.

In a study by researchers at Northwestern University in Evanston, IL, the scientists decided to look at both the level of methylation in the meningioma genomes and the number of repeats in different CNVs. They included certain genes in the cancer genome known to control growth and repair to see if this provided any insight into outcomes.

The findings are published in the journal Nature Genetics.

Using genomic data from 565 tumors taken from two cohorts of patients who had been followed up for 56 years, researchers profiled the DNA methylation of the cancer genomes. They then analyzed this alongside the presence of DNA repeats at certain points in the genome and also looked at the RNA present in the tumors to determine which genes had and hadnt been expressed.

They found that looking at the number of repeats within certain genes alone did not predict patient outcomes accurately, but looking at the number of repeats of genes alongside the level of methylation revealed three different grades of tumor.

Just over one-third of the tumors in the cohort were designated merlin intact meningiomas, where patients had the best outcomes. These tumors did not involve abnormal numbers of repeats on the gene that codes for a protein called merlin, which acts as a tumor suppressor. There was also normal methylation around this gene, allowing it to be expressed normally.

Conversely, 38% had immune-enriched meningiomas where patients had intermediate outcomes. These tumors were characterized by loss of the gene that codes for merlin and downregulation of other tumor-suppressing genes due to methylation.

This allowed them to overcome normal responses from the immune system.

A further 28% had hypermitotic meningiomas where the patient not only had fewer repeats of the gene that codes for merlin but a number of other gene repeats that caused either increased growth or decreased tumor suppression.

They also had methylation that allowed the increased expression of a gene known to promote cell growth. These patients had the least favorable outcomes.

Using this information, the researchers then tested the drug abemaciclib, a cancer drug already used for breast cancer, on tumor cells in cell lines, organoids, and xenografts in mice.

Results from these experiments indicated the drug could be used to treat individuals who had been identified as having either immune-enriched tumors or hypermitotic tumors.

Previously trials have failed to identify drugs that could reliably treat meningioma, but the identification of a biomarker could help identify patients who could benefit from certain treatments, said lead study author Dr. Stephen Magill.

Dr. Magill is an assistant professor of neurological surgery at Northwestern University Feinberg School of Medicine. He told Medical News Today in an interview: Some of our findings are really raising the possibility that the more we know about the biology, [the more] we can then say: this isnt just a meningioma, you have a hypermitotic meningioma.

So we can really use that as a biomarker to stratify who would go into a clinical trial.

Cancer researcher professor Noam Shomron from the Sackler Faculty of Medicine from Tel Aviv University, Israel, who was not involved in the research told Medical News Today:

I think its a wonderful study, because its so comprehensive, and it spans molecular and clinical findings and structural variations and methylation which is epigenetics [and something that] doesnt often take center stage.

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Brain tumor growth may be halted with breast cancer drug - Medical News Today

Additional safety data, including 12-month follow-up on all subjects, demonstrated GNSC-001 is safe and well tolerated

Injection of GNSC-001 was associated with increased synovial concentrations of IL-1Ra and improved pain and function scores

Osteoarthritis affects more than 30 million Americans, and is leading cause of disability

PALO ALTO, Calif., May 17, 2022 /PRNewswire/ -- Genascence Corporation ("Genascence"), a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, today announced that additional safety data from the Phase 1 clinical trial of GNSC-001 for the treatment of osteoarthritis (OA), including 12-month follow-up on all subjects, demonstrated that it was safe and well tolerated. These data will be delivered in a poster presentation today at the American Society of Gene & Cell Therapy's (ASGCT) 25th Annual Meeting being held virtually and in-person May 16-19, 2022, in Washington, D.C.

Genascence Corporation (PRNewsfoto/Genascence)

GNSC-001 is the company's lead program in OA. GNSC-001 is a genetic medicine a recombinant adeno-associated vector (AAV) carrying a coding sequence for interleukin-1 receptor antagonist (IL-1Ra), a potent inhibitor of interleukin-1 (IL-1) signaling. IL-1 is considered one of the key mediators involved in the pathogenesis of OA, causing inflammation as well as cartilage destruction. GNSC-001 is designed to offer long-term, sustained inhibition of IL-1 following a single injection into the affected joint.

"Osteoarthritis is incapacitating, causing years of pain and disability for people living with the disease. Further, patients have limited treatment options, and nothing is currently available that is able to slow down progression of OA," said Thomas Chalberg, Ph.D., founder and CEO of Genascence. "We are excited by these findings as they demonstrate the initial safety of GNSC-001 and provide encouraging data to pursue GNSC-001 as a novel treatment for OA patients. We look forward to advancing the clinical program for GNSC-001 so that we can deliver transformative results for patients suffering from this disabling disease."

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Title: A Phase I Trial of Osteoarthritis Gene Therapy (NCT02790723)Date: May 17, 2022 5:30-6:30 PM ETSession: Gene and Cell Therapy Trials in ProgressAbstract Number: 799Location: Walter E. Washington Convention Center, Hall DPresenter: Christopher H. Evans, Ph.D.

In this investigator-sponsored Phase 1 single-arm, open-label, dose-escalation clinical trial of GNSC-001, a total of nine subjects with knee OA were enrolled and monitored for one year. Three subjects were treated in each of three cohorts, receiving either 1x1011 vg, 1x1012 vg, or 1x1013 vg GNSC-001 delivered by intra-articular injection. The primary endpoint is safety and tolerability. Additional measures include levels of circulating viral genomes, immune response to the vector, blood and urine analysis, and physical examination. Although the study was not powered for efficacy and had no control group, patients reported pain via VAS (0-10) and pain and function via WOMAC. Knee joints were imaged by X-ray and MRI upon study entry and after one year.

Results showed that intra-articular injection of GNSC-001 produced no severe adverse events; blood chemistries and hematologies remained normal during the 12-month follow-up period with no evidence of neutropenia. There were no vector-related adverse events in eight of the nine subjects; one subject experienced a mild/moderate knee effusion following injection which resolved with ice and rest. Clinical trial participants developed various degrees of anti-AAV neutralizing antibodies after injection of GNSC-001, as seen in preclinical studies. Small amounts of viral genomes were found in peripheral blood, beginning one day after injection and clearing within four weeks. Injection of GNSC-001 was associated with increased concentrations of IL-1Ra in synovial fluid, which remained elevated after 12 months of follow up. Pain and function scores improved following injection of GNSC-001.

"These additional data from the Phase 1 trial of GNSC-001 in patients with osteoarthritis showed that it safe and well tolerated including after one year," said Dr. Evans. "These results are encouraging as we believe this therapy has the potential to reduce structural disease progression in osteoarthritis patients."

The study was supported by funding from the U.S. Department of Defense Peer Reviewed Medical Research Program (PRMRP). More information is available at https://clinicaltrials.gov/ct2/show/NCT02790723.

Abstracts can be accessed via the conference website at annualmeeting.asgct.org.

About Osteoarthritis (OA) of the Knee

Osteoarthritis (OA), or degenerative joint disease, is the leading cause of disability. It is characterized by destruction of cartilage and structural changes in bone within the joint, which contribute to pain and loss of joint function. Osteoarthritis affects more than 30 million Americans and is increasing as a result of the aging population and increasing prevalence of obesity. Osteoarthritis represents a major economic burden, owing to direct medical costs and loss of productivity. Each year, millions of patients are treated for knee OA with NSAIDs, opioids, and steroid injections into the knee to manage their knee pain. There are no currently available therapies known to alter or slow down OA progression.

About Genascence Corporation

Genascence, a clinical-stage biotechnology company revolutionizing the treatment of prevalent musculoskeletal diseases with gene therapy, is developing life-changing treatments for highly prevalent conditions affecting millions of people. The company was founded in 2017 with technology licensed from three leading U.S. research institutions: Mayo Clinic, University of Florida, and NYU Langone Health. Headquartered in Palo Alto, California, Genascence's founders and leadership team have deep experience in the design, development, and manufacturing of successful gene therapies and biological medicines. For more information, please visit http://www.genascence.com.

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Genascence Announces Data From Phase 1 Clinical Trial on GNSC-001, Company's Lead Program in Osteoarthritis, Presented at American Society of Gene...

Multiple adaptable DNA sequence-encoded human genetic elements are modality-agnostic and can be combined to customize expression profiles to optimize therapeutic approaches in and beyond the brain

SOUTH SAN FRANCISCO, Calif., May 18, 2022--(BUSINESS WIRE)--Encoded Therapeutics announced nonclinical data being presented today at the American Society for Cell and Gene Therapy 25th Annual Meeting showing how its proprietary human genomic regulatory element (RE) engineering platform has been used to develop cell-selective expression vectors for targeted gene therapy. The company efficiently discovered a spectrum of sequence-encoded genetic elements, including enhancers, promoters and UTR elements, that drive selective expression profiles in mice. These REs function within the size constraints and episomal architecture of adeno-associated viruses (AAVs) and are compatible with multiple capsids and gene delivery systems.

"By combining human genomic regulatory elements to customize expression profiles and minimize off-target effects, we aim to improve the safety and efficacy of gene therapies for a broad range of monogenic and non-monogenic diseases in the future," said Encoded CEO Kartik Ramamoorthi, Ph.D. "Our regulatory elements engineering approach increases cell-selective expression, reducing toxicity concerns in tissues like the liver. The data were sharing today at ASGCT are exemplary of the Encoded platforms ability to achieve appropriately targeted transgene expression across many other central nervous system (CNS) cell types, like dorsal root ganglia (DRG) neurons, as well as non-CNS cell types."

Using Encoded's genomic medicine platform, researchers applied both expression-based functional screening and computational modeling to simultaneously test thousands of genomic elements in vivo. They uncovered sequence elements that selectively decrease liver expression while maintaining CNS expression in mice. Additionally, the research team constructed predictive models to rapidly and iteratively continue to improve the discovery rate and distribution of activity profiles, resulting in further reduction of liver expression in mice, with unchanged expression in the brain.

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Click here for the abstract of Encodeds ASGCT presentation, "Optimized Human Regulatory Sequences Achieve Targeted Expression in CNS and Decreased Liver Expression in Mice."

About Encoded Therapeutics

Encoded Therapeutics is creating one-time, disease-modifying gene therapies for pediatric central nervous system (CNS) disorders with its cell-selective targeting and regulation platform. The Encoded approach offers unprecedented gene specificity and cell selectivity to unlock novel opportunities by targeting a range of disease mechanisms. Encodeds technology is compatible with any delivery system to control where and when therapeutic transgenes are expressed, thereby shaping the functionality of target cells and holding broader therapeutic potential beyond CNS disorders. For more information, please visit http://www.encoded.com, and follow us on LinkedIn, Twitter @EncodedTx and YouTube.

View source version on businesswire.com: https://www.businesswire.com/news/home/20220518005469/en/

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Lynnea Olivarezlolivarez@encoded.com 956-330-1917

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Encoded Therapeutics Presents Nonclinical Data Showing Genomic Medicine Platform Yields Selective Expression to Optimize Gene Therapy Performance at...

NEW YORK California, the nation's most populous state, recently began coveringrapid diagnostic whole-genome sequencing (rWGS) for sick infants under Medicaid. The decision, in theory, should make the test more widely available, leading to faster diagnoses, better medical decisions, and lower healthcare costs in many cases.

On Jan. 1, a provision of a state budget bill from 2021 kicked in, expanding Medi-Cal benefits to include rWGS for beneficiaries under 12 months old who are receiving inpatient hospital services in an intensive care unit.

California is one of at least five states that now proclaim to cover that form of diagnostic testing as part of their health programs for low-income residents, expanding access to tens even hundreds of thousands of babies. Michigan was the first to do so in September of last year, while Oregon and Maryland joined California in offering coverage beginning Jan. 1 and Minnesota startedcoverage April 4. The states are following private payor Blue Shield of California, which has covered rWGS for critically ill newborns since June 2020.

Support for this policy from state governments comes as studies are providing more evidence that rWGS can improve medical care often abbreviating the so-called diagnostic odyssey and can even save money. Data from SeqFirst, a study of rWGS with broad inclusion criteria, have echoed the diagnostic yield of around 40 percent seen in Project Baby Bear, a pilot study funded by the state of California. In addition, cost analyses of providing rWGS to children older than one year suggest there are savings to be found in those cases, too.

"Genomic sequencing should more often be the first DNA test that is sent [out], and rapid WGS should be the standard of care when a child is hospitalized," said Erica Sanford Kobayashi, a pediatrician at Cedars-Sinai in Los Angeles who worked on Project Baby Bear while at Rady Children's Hospital in San Diego. And the faster, the better: Results should ideally be delivered within three days, she said, with no cost savings associated with 14-day turnaround.

Whether children will actually receive this diagnostic testing remains to be seen. "Anecdotally, [NICU doctors] are having a hard time ordering these tests," said Paul Kruszka, chief medical officer at GeneDx, a genetic testing company recently acquired by Sema4 that offers rWGS services, and an investigator on the SeqFirst study. Many doctors without clinical genetics training are simply not comfortable doing so, he said, noting that identifying patients, managing consent, and interpreting and delivering results are key challenges.

Moreover, byzantine medical billing rules mean that hospitals in California and potentially elsewhere may not be able to access the funding theoretically available for rWGS in the NICU under Medicaid.

California led the way in studying the potential benefits of sequencing the genomes of inexplicably ill newborns when it launched Project Baby Bear in 2018, providing $2 million for a pilot study in collaboration with Rady Children's Hospital and several other sites. Other states, including Michigan and Florida with Projects Baby Deer and Manatee, respectively, have run their own pilot programs.

Baby Bear showed that sequencing the genomes of 178 parent-child trios resulted in 76 infants receiving diagnoses 35 of them rare conditions that occur in less than one in a million births. Of those, 55 saw a change in treatment or management, resulting in a combined 513 fewer hospital days, 11 fewer major surgeries, and a reduced testing burden that alone saved an estimated $300,000. Other costs were reduced by approximately $2.5 million, mostly attributable to shorter hospital stays, according to Sanford Kobayashi.

In a study of cost-effectiveness of rWGS published in January in Frontiers in Pediatrics, she wrote that trio sequencing costs approximately $7,500, including interpretation. However, the figure is "an average of total costs from previous cases sequenced at Rady," the authors noted.

Rady provides rWGS testing for itself and about 80 other hospitals, charging around $8,000 to $9,000 for sequencing and interpretation. "We have a bespoke, extremely rapid test," said Stephen Kingsmore, director of the Rady Children's Institute of Genomic Medicine and a champion for rWGS in pediatrics. "It can be done for less, but it's the difference between a Rolls-Royce and a Ford Fiesta."

Other state "baby animal" programs saw comparable results. Baby Manatee, led by Nicklaus Children's Hospital in Miami in collaboration with Rady Children's, enrolled and sequenced the genomes of 50 patients, leading to 20 diagnoses (diagnostic yield of 40 percent) and a change in care for 19 patients, or 38 percent. The estimated savings were more than $3.8 million a $2.9 million return on investment, according to the final report.

For the 89 children in the Baby Deer study, 35 received a diagnosis (39 percent yield) with 24 (27 percent) receiving a change in management. At least 95 hospital days were avoided, contributing to total savings of $252,938.

In general, across 12 studies looking at the impact of rWGS on care of critically ill newborns, the diagnostic rate was 35 percent, with up to 77 percent of those patients receiving a change in management, Sanford Kobayashi said at a presentation in February at the Molecular Tri-Con meeting in San Diego.

The specific Medicaid benefits available for rapid diagnostic genome sequencing in infants and the ordering criteria vary by state. For example, in Michigan, rWGS requires prior authorization and isn't covered when the patient has an infection, trauma, or a confirmed pre- or postnatal genetic diagnosis, among other reasons. The state covers $6,278 in costs for rWGS testing specifically from Rady Children's, or $4,165 for the more general procedure of WGS billed under current procedural terminology (CPT) code 81425, "Genome (e.g., unexplained constitutional or heritable disorder or syndrome); sequence analysis" and $2,243 for CPT 81426, the code for comparator genomes, such as the parents. The state also covers genetic counseling. For fiscal year 2019, Medicaid covered approximately 46 percent of the 109,000 total births in Michigan.

Maryland also requires prior authorization and reimburses $3,999.80 for CPT 81425 and $2,154.40 for CPT 81426, according to data provided by Illumina. In 2020, the state had 68,554 newborns, of which nearly 40 percent were covered by Medicaid.

Minnesota requires an evaluation by a medical geneticist "or other physician subspecialist with expertise in the conditions or genetic disorder for which the testing is being considered," a spokesperson for the state's Department of Human Services said in an email.

Oregon, which already covered whole-exome sequencing under Medicaid for children under 18, may also cover rWGS for children over the age of 1 "if, based on individual consideration by the plan, the test will benefit the patient in terms of growth, development, or ability to participate in school," Philip Schmidt, a spokesperson for the Oregon Health Authority, said in an email. Data provided by the state showed that the Oregon Health Plan covered 53 WES tests during 2020. No data were available yet on rWGS coverage.

While California budget acts are only law for one year, the coverage expansion was included in a budget trailer bill, according to Nannette Miranda, director of communications for Assemblymember Phil Ting, D-San Francisco, chair of the budget committee. "Trailer bills become permanent law, just like regular bills," she said. Rady Children's hired lobbyist John Valencia to help get rWGS covered, she noted. The state's 2021-2022 budget provided $6 million to cover such testing, although it is not clear how much, if any, has been used. The state estimates that Medi-Cal covers around four in 10 children, and in 2020, the state had approximately 420,000 births.

In both Oregon and Maryland, San Diego-based Illumina helped precipitate the coverage decisions. Minutes from a Nov. 18, 2021, virtual meeting of Oregon's Health Evidence Review Commission, which makes coverage policy decisions for new treatments or procedures for the Oregon Health Plan, noted that "recently, Illumina contacted HERC staff to request a review of coverage of WGS." HERC had last considered the test in 2014. Illumina Senior Medical Director for the Americas John Fox, a veteran of Project Baby Deer, also testified at the meeting.

"Both Illumina and many supportive providers wrote the state [of Maryland] asking them to expand coverage for this important innovation," Illumina Senior Director of Communications Adi Raval said in an email. "We are grateful to the state for its action in a year of significant evolution, with COVID and other issues demanding their limited time."

Illumina's market access teams are pushing to get rWGS covered in other states, including Iowa and Ohio, as well as in other countries. "What we found is, if Illumina does not take the lead, it's very hard to accelerate adoption in the marketplace," said Ammar Qadan, Illumina VP of global market access.

Aside from the state-funded studies, other results are supporting the expanded use of sequencing in newborn care. At the American College of Medical Genetics and Genomics annual meeting in March, researchers from the SeqFirst study which received donated sequencing reagents from Illumina presented data suggesting that more than half of the 125 study participants received an abnormal result that led to an explanatory, or at least partially explanatory, diagnosis.

"Two-thirds were suspected of having a genetic disorder, but one-third were not," said Mike Bamshad, chief of genetic medicine in the pediatrics department at the University of Washington and Seattle Children's Hospital, and principal investigator on SeqFirst. Of that one-third, nearly all (93 percent) saw a change in management.

The premise of the SeqFirst study is to improve access to precision genetic diagnostics. There are only a few reasons not to do sequencing, GeneDx's Kruszka suggested. For the study, children are only excluded if their illness can be explained by infection, trauma, or prematurity.

The researchers had hypothesized that by expanding enrollment, the diagnostic yield would drop, potentially by as much as 50 percent. "So we were impressed that our explanatory rate remained up around 50 percent," Bamshad said.

"These are results that scream to me 'we need to look at a much larger population of kids,'" he said. "Clearly, this strategy does exactly what it's intended to do."

SeqFirst, through GeneDx, was able to deliver verbal results in an average of five days, Kruszka said. But according to Sanford Kobayashi, results need to come back more quickly to yield the full benefit of testing.

"Project Baby Bear showed that savings are influenced by test turnaround time," she said. The best outcomes come when results are back in three days or less, she added. "If you want to have the biggest impact, it does have to be that fast."

While ultra-rapid sequencing in the NICU may yield the most medical and economic benefits, "diagnosis is beneficial at any stage in life," Sanford Kobayashi said. Her new research is focused on using rWGS in the pediatric intensive care unit, which admits older children.

"All the kids born 10 years ago with maybe long QT syndrome or cardiomyopathy, they're still showing up to the PICU," she said. "Until we catch up and start sequencing everybody earlier, there are still going to be years where it would be useful to apply it to older children."

In the cost-effectiveness study published in January, Sanford Kobayashi's team assessed the cost of sequencing in the pediatric, rather than neonatal, ICU. Of the 38 participants, 17 received a diagnosis from WGS and seven had a change in management, allowing the team to model costs for them. While such cost modeling for rare disease is hard, because there are not always good data to compare to, the team used a so-called "Delphi consensus method" that compared the children to a counterfactual trajectory a hypothetical scenario in which rWGS was not ordered. Each trajectory was sent to 10 different pediatric institutions for review. "In doing that, we found that we saved about $185,000 in hospital costs," she said, again mostly due to shorter stays. Sequencing the trios cost about $240,000, resulting in net spending of about $55,000. Moreover, the study found that WGS added a total of about 12 quality-adjusted life years (QALY), an advanced metric that seeks to quantify the value of medical procedures beyond the simpler calculation of extended survival. "We were spending about $4,500 per QALY, which is super reasonable," she said, adding that spending $50,000 to get just one QALY is considered cost effective.

Still, most of the benefits of rWGS in older children are concentrated in a small number of cases. One of the children in the study was a 9-month-old who had been admitted to the PICU "without a good reason." Imaging showed a brain bleed and WGS detected a factor 13 deficiency, a hemophilia-like rare disease that is very unlikely to be tested for. Later, the child fell off a couch and was given extra factor 13 as part of the treatment, preventing another brain bleed.

"The moral of the story is that there are going to be times we dont make a diagnosis and it doesn't save any money," Sanford Kobayashi said. "But often enough, you're going to make a big enough impact that it makes up for those other times."

When asked why Oregon's HERC decided not to cover rWGS for children over 1, even though it covers WES for them, a spokesperson said, "the Commission decided that this group of patients (severely ill hospitalized infants) would have the clearest benefit from this service, because it would be most likely to affect treatment planning for this group."

"If the evidence for WGS for older, less severely ill children develops in the future, the HERC will consider expanding coverage beyond the group that is currently covered," she said.

While states are saying they'll cover this testing, there's still no guarantee that the children who need it will have it ordered for them. "Eventually, most big children's hospitals will do their own WGS," Sanford Kobayashi said. "But it's a big lift. The equipment is expensive, and people who can do the analysis are expensive."

Also, most doctors are not experts in genetic medicine. "We're not training a whole lot of medical geneticists," Kruszka said. "There are fewer than 60 residency slots per year and only half are being filled."

Even in the best-case scenario, where a patient is in the NICU, often the ordering physician will not have expertise in genetics. Those doctors continue to express discomfort ordering a test that requires consent and the results of which need to be explained and put into context, Kruszka said. And that doesn't even begin to address ordering the test outside of ICUs.

The good news is that when doctors see the power of rWGS up close, they're easily sold. "When neonatologists start using the technology, they love it," Kruszka said.

"Intensivists are eager to see us scale up," Bamshad added. "In the end, we're making their workflows much easier. And the changes in [patient] management are sometimes profound. They're now concerned theyve been missing things all along."

The SeqFirst researchers suggested that relying on clinical geneticists will only hinder access and are now considering ways to help nonexperts, possibly with handheld devices that help navigate the explanation and consenting process.

"Interpreting the result is key," Bamshad said. "That is probably done most effectively face to face with a genetics provider. To be honest, we probably still don't have the workforce to do that." At Seattle Children's, wait times to be admitted to the genetics clinic can be a year, even two; the hospital also has nearly two dozen genetic counselors to help interpret results. "That's a luxury that doesn't exist in most places," he said. "Eventually, we'll have to get to a point where return of this information is facilitated by technology and interpretation is done by nonspecialists."

Expanding the practice area for genetic counselors may be part of the answer. Michiganis in the process of licensing genetic counselors as independent clinicians, which could happen this year, Bob Wheaton, the spokesperson for the Michigan Department of Health and Human Services, said in an email. "Once this occurs, Medicaid will begin enrolling these practitioners and will allow direct reimbursement of genetic counseling services."

At the federal level, there are two avenues that could lead to increased coverage for rWGS in newborns under Medicaid. Last year, USSens.Susan Collins, R-Maine, Mark Kelly, D-Ariz.,and Bob Menendez, D-N.J.,introduced the "Ending the Diagnostic Odyssey Act," which would have the federal government pay 75 percent of the cost of rWGS, with states picking up the rest.

The 21st CenturyCures 2.0 bill, introduced last November by US Rep. Diana DeGette, D-Colo.,also could lead to funding of "demonstration projects" in up to 15 states.

But unless the mechanisms by which Medicaid pays for inpatient care are addressed, hospitals are unlikely to facilitate ordering of rWGS in the NICU.

States reimburse for hospital stays with diagnostics-related group (DRG) payments, essentially a lump sum for a particular type of hospital stay. "As a genetics physician, that puts us in a tough spot," said Caleb Bupp, a physician at Helen DeVos Children's Hospital in Grand Rapids, Michigan, and a leader of Project Baby Deer. "The cost of genetic testing eats up how much the hospital gets reimbursed," he said, potentially resulting in a net loss. "My perspective is, [rWGS] only works if payment happens separately. That's the elephant in the room."

In Michigan, the state created a DRG "carve-out," a pipeline to directly fund rWGS testing in the NICU, which takes the onus for the cost of testing off hospitals. Getting that carve-out, however, was only possible due to trust that the various parties, including the state health department, had built up after years of dialogue, Bupp said. "You have to call it out as something you problem-solve for," he said.

California does not have a DRG carve-out, Kingsmore said, and Minnesota has not made one, either. "The performing lab outside the hospital would submit for the test," the DHS spokesperson said. Whether Oregon and Maryland have carve-outs is not clear state health departments did not immediately respond to follow-up questions about payment mechanisms.

States that have not addressed payment for rWGS "are stealing from themselves by disincentivizing doctors from ordering this test," Kingsmore said. "It's really bizarre; they're saying 'no' to something that would save them money."

Rady has scheduled meetings with the California Department of Health Care Services to address payment mechanisms, but any celebration about establishing rWGS coverage would be premature.

"We have additional work to do," Kingsmore said. "Without such payment, uptake will be essentially zero."

Link:
California, Other States to Cover Rapid WGS of Newborns Under Medicaid, but Questions of Access Loom - GenomeWeb

Dominik Magdziak Photography/Getty Images

The technological revolution that followed the Human Genome project is arguably the greatest thing to happen to medicine since penicillin. Since the project, new ways are developed daily to deeply investigate what is already known, including genetic mechanisms.

Immersed in one of these investigations is Ph.D. candidate Maxwell Serowoky working within the University of South Carolinas Stem Cell laboratory of Francesca Mariani, Ph.D. Serowoky observed an increase in Sonic Hedgehog (Shh) gene activity during rib bone recovery, expanding the genes function beyond the known role of embryogenesis. The findings were published this week in NPJ Regenerative Medicine.

The research team ran with Serowokys observation. After finding the increase in Shh expression, hypothesis testing with mouse models began. A 3 mm rib bone resection procedure was performed on the subjects. Over the course of 28 days post-resection, the researchers observed the progression of cartilage callus formation over the bone gap. This callus indicates bone recovery and regrowth, a trait seen in humans and mice. Over time, this cartilage converts to bone.

During the resection procedures, Shh activity was observed, quantified and compared to non-injured mice. The non-injured mice expressed Shh at low levels in only the bone marrow. In the experimentally injured mice, Shh was seen at high levels in mesenchymal cells near the resection on day three. The increase in Shh was also seen in neighboring skeletal muscle tissues and periosteal tissues. The increased expression levels peaked and waned at five days post-resection. Five days of Shh upregulation is hypothesized to be directly linked to the formation of the cartilage callus.

Additional data was collected as the researchers harvested and analyzed the rib tissue surrounding the resected region. Here, it was determined that the number of mesenchymal cells that were expressing high levels of Shh reached approximately 94% on day five. Shh expression was seen at lower levels in tissues slightly farther from the surgical site but remained detectable.

The researchers were able to examine the progression of healing through Safranin-O staining and H&E staining, ideal processes for examining tissues and cartilage. After staining, the regions were measured to determine the progression of healing between day 7 and day 28. This data was used alongside Shh expression quantification to support the overall conclusion: Shh upregulation is required for the formation of the cartridge callus that goes on to regenerate bone after injuries.

When scientists identified the Sonic Hedgehog gene, named after a hedgehog variation, much like the Indian hedgehog and moonrat hedgehog genes discovered prior, they couldnt have understood the importance of the video-game namesake. The initial observation of Shh in fruit flies revealed the genes role in embryogenesis, but over forty years elapsed before the genes capabilities were expounded upon. In 2018, stimulation of the Shh pathway was seen to trigger hair regrowth. Abnormal activity of the pathway may play a role in tumor cell aggression, according to St. Jude Childrens Hospital in 2016. What could the next forty years hold?

Read more from the original source:
Researchers Identify Role of 'Sonic the Hedgehog' Gene in Bone Repair - BioSpace

I was all for it, Malcolm said. So was Martin.

When they were tested, the brothers learned they had the variants and that the variants, not lupus, most likely were damaging their kidneys. They hardly knew how to react.

I am still trying to grapple with it, Malcolm said.

But Dr. Olabisi was not surprised. Researchers think the variants cause kidney disease only when there is a secondary factor. A leading candidate is the bodys own antiviral response, interferon, which is produced in abundance in people with lupus.

High levels of interferon also occur in people with untreated H.I.V. As happens in people with Covid-19, they can suffer an unusual and catastrophic collapse of their kidneys if they have the variants. Other viral infections, including some that may go unnoticed, can elicit surges of interferon that could set off the APOL1 variants. Interferon is also used as a drug to treat some diseases including cancer and was tested as a treatment for Covid patients.

For now, there is little Malcolm and Martin can do except take medications to control their lupus.

Martin said he understands all that, but hes glad he learned he has the variants. Now, he knows what he might be facing.

Im the kind of person who likes to plan, he said. It does make a difference.

While Dr. Olabisi is waiting to start his study, a drug company, Vertex, has forged ahead with its own research. But there was no agreement on how APOL1 variants caused kidney disease, so it was not clear what a drug was supposed to block.

If you dont understand the mechanism, that means you cant measure effects in a lab, said Dr. David Altshuler, chief scientific officer at Vertex. And if you cant measure effects in the lab, that means you cant correct them.

It was known how the APOL1 protein protected against sleeping sickness it punched holes in the disease-causing trypanosomes, making them swell with fluid and burst.

Link:
Targeting the Uneven Burden of Kidney Disease on Black Americans - The New York Times