StemCell Therapy

The 3rd annual Bakersfield Walk to Cure Arthritis event will take place Nov. 16 at The Park at River Walk. The event is put on to help find a cure for arthritis and to help people with arthritis live a full life, according to a press release.

"Arthritis is more than just a few minor aches and pains. It's a debilitating disease that robs people of their dreams," saidMichal W. Wiesbrock, executive director for Arthritis Foundation Central Coast, in a statement. "When you support Walk to Cure Arthritis, you become a Champion of Yes, helping us build a lifetime of better, while accelerating the search for a cure."

The walk features two local honorees on the front lines in the battle against arthritis. This year the 2019 Medical Honoree is Dr. Andrew A. Kao, and the 2019 Youth Honoree is Leila Shackleford, according to the release.

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Bakersfield Walk to Cure Arthritis to take place in November - The Bakersfield Californian

Video telemedicine may be anoption for care inrheumatoid arthritis (RA) for patients who have high disease activity andpositive perceptions of telemedicine, and for physicians who frequently utilizetelemedicine technologies, according to research published inArthritis Care and Research.

Using data from patients within the Alaska Tribal Health System, researchers sought to determine the baseline factors associated with the use of telemedicine for RA. Adults 18 and older with an RA diagnosis who were seen at the Alaska Native Medical Center between August 2016 and March 2018 were invited to participate in the study.

Throughout the baseline enrollment period,rheumatology-specific telemedicine was available in the form of synchronousvideo teleconference. Physicians were briefly and generally trained on the useof the telemedicine equipment. Telemedicine was made available to patients in 2different scenarios: Those residing in rural areas could use the videoteleconference to reduce travel burden, or care was provided at the AlaskaNative Medical Center in Anchorage from a rheumatologist who wasvideo-conferenced in from out of state.

In total, 122 patients participated in the study. In boththe telemedicine and in-person groups, patient demographics were similar withrespect to age, sex, and disease duration (mean 10 years). A majority ofparticipants across both groups had positive autoantibodies (>85% positivefor rheumatoid factor and anticyclic citrullinated peptide), and almost allpatients had been prescribed disease-modifying antirheumatic drugs within thelast year.

Both groups had a mean number of rheumatology visits withinthe past year higher than 2; however, the telemedicine group had more visitsoverall (mean 2.95 vs 2.39;P=.011).The telemedicine group also had higher survey scores, which indicated morepositive perceptions of telemedicine and a higher mean rheumatologisttelemedicine rate, indicating that they were seeing a rheumatologist whoperformed telemedicine visits more frequently.

Investigators conducted a multivariate analysis for age,sex, number of rheumatologist visits in the past year, Routine Assessment ofPatient Index Data 3score, telemedicine survey score, ever seen bytelemedicine by any provider, and mean rheumatologist telemedicine rate. Thestrongest association with patient use of telemedicine was the meanrheumatologist telemedicine rate (odds ratio [OR] 4.14; 95% CI, 2.35-8.00).Additional strong associations were observed between the telemedicineperception survey score and use of telemedicine (OR 2.76; 95% CI, 1.32-6.18),the number of rheumatologist visits in the past year, and Routine Assessment ofPatient Index Data 3 score.

In addition, patient perceptions of telemedicine were an important factor associated with the choice to use telemedicine for RA follow up vs in-person care only. Survey results indicated that patients who had ever been seen by telemedicine responded more favorably than those who had not. Overall, patients still preferred to be seen by a specialist in person, regardless of group (61% of the telemedicine group and 74% of the in-person-only group), but those in the telemedicine group were more likely to feel that care provided via video was as good as care provided in person.

Limitations to the study included the observational natureof the research, possible unmeasured staff or provider biases that contributedto patient choice, and the unique setting that may prevent a generalization ofresults to other populations.

Future studies will investigate disease activity over time and quality of care for RA in the setting of telemedicine compared [with] usual care and will help inform practice further, the researchers concluded.

Reference

Ferruci ED, Holck P, Day GM, Choromanski TL, Freeman SL.Factors associated with use of telemedicine for follow-up of rheumatoid arthritis[published online August 17, 2019].Arthritis Care Res.doi: 10.1002/acr.24049

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Rheumatoid Arthritis Care and the Option of Telemedicine - Rheumatology Advisor

LANSING Dr. Karen Kent VanGorder sees a lot of patients who aren't compelled to manage their health because they don't have troubling symptoms.

"The mostcommon thing I hear as a doctor is someone looks at me and shrugs and says, 'I feel good," VanGorder, who servesas Sparrow Health System's chief medical officer, said.

That can be an issue with chronic conditions like high cholesterol that often don't have symptoms until they lead to major issues like stroke or heart attack, she said.

VanGorder saidshe tries to help patients understand "the natural history of a chronic condition absolutely applies to them" and they need to think about how they'll feel in 10, 15 or even 20 years.

"Lucky is not a plan," she said.

VanGorder works to motivate patients to eliminate risk from their life, comparing it to teaching a kid to look both ways before crossing the street and she said the good news isthat it can besimple.

It can be as easy as walking every day, she said, stressing that increasing activity is free and doesn't require an appointment or insurance.

"The more we move in mid-Michigan, the healthier we're going to be," she said.

And people's health does impact the community in various ways, VanGorder said.

When people have chronic conditions, it affects family, friends, co-workers, neighbors and more, she said.

And according to a state survey that tracks the prevalence of medical conditions, among other topics, some of those conditions affect around a third of the adults in the Lansing area.

People with high cholesterol and high blood pressureare much more likely to have a heart attack, stroke or another vascular issue because of damage to blood vessels.

Prevalence: According to the Centers for Disease Control, 68 million American adults a little less than 33% have high cholesterol and about 32% have high blood pressure.

Show caption Hide caption Michael Ranville, 74, of Charlotte, works out Wednesday, April 25, 2018, at ALIVE! in Charlotte. He suffered a massive heart attack in 1984, and...Michael Ranville, 74, of Charlotte, works out Wednesday, April 25, 2018, at ALIVE! in Charlotte. He suffered a massive heart attack in 1984, and had a heart transplant in 2015. Ranville works out for 35-40 minutes three days a week.MATTHEW DAE SMITH/Lansing State Journal

Issues with both cholesterol and blood pressure are more common in Michigan. According to data from the Michigan Department of Health and Human Services, 36.5% of Michiganders have high cholesterol and 33.9% have been diagnosed with hypertension.

High cholesterol ratesUSA Today Network

Regionally, it's about as prevalent 36.7% of people in the Lansing area and nearby counties said they have had their cholesterol checked within the last five years and had a health professional tell them they have high cholesterol. And 35.1% of respondents in the Lansing area said a health professional has told them they have high blood pressure.

It's more prevalent in Barry and Eaton Counties, where 41.4% of respondents self-identified as having high cholesterol and43.4% said they've been diagnosed with high blood pressure.

Issues with cholesterol and blood pressure are least prevalent in Ingham County, where 34.6% of people said they've been diagnosed with high cholesterol and30.2% of respondents indicated a health professional has told them they have high blood pressure.

Cost: According to a study published last year in the Journal of the American Heart Association, adults with high blood pressure spend nearly $2,000 more each year on health care.

According to that same study, health care for adults with high blood pressure costs an extra $131 billion annually than it does for those without hypertension.

Another report commissioned by the American Heart Association found that in 2010, heart disease cost the country $273 billion in direct medical costs and $172 billion in lost productivity.

High blood pressure ratesUSA Today Network

Treatment and Prevention: Lifestyle plays a major factor in people's cholesterol and blood pressure levels. To help avoid or manage either condition, people can:

People with high blood pressure also can benefit from reducing stress, limiting how much alcohol they drink and eating food that's rich in potassium, including fruits like bananas and oranges, cooked vegetables like broccoli and spinach and some fish such as tuna and trout.

When lifestyle changes aren't enough, medication can help. Drugs known as statins are the primary medication used to treat high cholesterol.

There are many more types of drugs that can treat high blood pressure, from diuretics that get rid of excess sodium to beta-blockers that reduce heart rate to vasodilators that relax the walls of blood vessels.

Impact on everyday life: Hear from Dr. Awais Kang, a cardiologist with McLaren Greater Lansing, about helping patients with high cholesterol and high blood pressure avoid more serious heart problems and regain heart function.

Heather Tompkins-Herber talks about managing her arthritis Friday, Oct. 18, 2019.Robert Killips | Lansing State Journal

Prevalence: About 23% of Americans have arthritis, according to the CDC.

The inflammatory disorder is more common in Michigan, where 30.8% of respondents to a statewide survey say a health professional has diagnosed them with arthritis.

And it's about as common in the Lansing region, with 29.5% of respondents saying they've been diagnosed.

It's more common in Barry, Eaton, Clinton, Ionia and Montcalm counties, where 33.5% of people said they have arthritis.

Arthritis ratesUSA Today Network

And it's less common in Ingham County, where 26.3% of respondents said a health professional has diagnosed them with arthritis.

Cost: According to a study published in 2017, adults with arthritis spent an extra $2,117 in medical costs and missed out on $4,040 in potential wages each, on average, in 2013.

Nearly half of all medical costs went to outpatient care, which can include diagnosis, consultation, treatment and rehabilitation.

Treatment: There are various ways to treat the symptoms of arthritis.

Some might opt for medication. Most drugs used to treat arthritis help relieve pain and inflammation.

Others might choose to take supplements and herbs to treat pain, stiffness and inflammation or opt for other treatments like massage or electrical stimulation as an alternative to drugs.

Joint surgery and otherprocedures arealso an option, but areusually recommended only after trying other treatment methods.

Prevention: According to the Arthritis Foundation, there's no sure way to prevent the condition.

But there are ways to reduce risk factors and delay the potential onset of any of the various 100 forms of arthritis, including:

Impact on everyday life: Learn how Heather Tompkins-Herber, a Charlotte residentdiagnosed with arthritis in her early thirties, manages nearly constant pain in her neck and spine.

Prevalence: According to the CDC, 7.7% of Americans have "current asthma." That means they've been diagnosed with asthma at some point in their life and have been told they still have the condition.

Asthma is more common in Michigan, with 10.7% of survey respondents saying they still struggle with the condition.

Eric Ware, of Lansing, pictured with medicines he must carry in case of an asthma attack. He has battled asthma since he was 5.Matthew Dae Smith/Lansing State Journal

Locally, it's less common in Clinton, Ionia and Montcalm counties, where 8.1% of respondents say they still have asthma.

It's more common in Ingham County, where 12.1% of people say they have current asthma.

Cost: A CDC study published last year found the total annual cost of asthma including medical care, absenteeism and mortality was $81.9 billion.

That breaks down to $3,266 per person, on average:

The study found adults with asthma missed a combined 8.7 million work days and lost an average of $214 in potential earnings.

Treatment: There are a variety of medicines that can help people control their asthma.

The American Lung Association breaks them into five categories:

Asthma ratesUSA Today Network

Prevention: According to the Mayo Clinic, it isn't clear why some people get asthma and others don't, but there are risk factors that might increase the chance of getting asthma.

Some of those you can't necessarily control, such as whether a parent or sibling has asthma or whether you have an allergic condition like eczema.

Others, though, are based on behavior or environment:

The U.S. has third-highest rate of child asthma cases linked to traffic-related air pollution

A shocking 4 million cases of children developing asthma per year could stem from traffic-related air pollution.

Buzz60

Impact on everyday life: Eric Ware was diagnosed with asthma at 5. Learn about how he's managed it, including just accepting it as a lung disease.

Prevalence:According to the CDC, 9.3% of American adults have diabetes.

State figures show it's more common in Michigan, with 11% of survey respondents saying they've been diagnosed with either Type 1 or Type 2 diabetes.

It's slightly less common in the region, with 10.3% of people surveyed saying they have diabetes.

That's swayed by Ingham County, where it's much less prevalent 7.9% of people said they've been diagnosed with diabetes.

It's more common in Barry and Eaton counties, where 13.4% say they've been diagnosed, and Clinton, Ionia and Montcalm counties, where 12.2% say they have either of the two main types of diabetes.

Cost:According to the American Diabetes Association, people with diabetes have medical expenses about 2.3 times higher than those without diabetes.

ADA organization estimates diagnosed diabetes costs around$9.7 billioneach year in Michigan alone, based on data from 2017:

Treatment: People with any type of diabetes need to check their blood sugar levels multiple times a day. Treatment, though, can vary from person to person.

Diabetes ratesUSA Today Network

Some people can manage their diabetes with healthy eating and exercise. Others need to take medication to lower their blood sugar or inject prescription insulin to help their body regulate blood sugar levels by either using or storing glucose.

Prevention: Different kind of diabetes have different causes, including the most common Type 1 and Type 2.

The American Diabetes Association identifies two factors that are key in causing both types: Inheriting a predisposition to the disease and environmental triggers.

For example, research has shown people who live in places with cold climates develop Type 1 diabetes more often, but in most cases, people also need to inherit risk factors from both parents.

Lifestyle is more influential in developing Type 2 diabetes. Studies have shown those at risk of developing Type 2 can delay or prevent it with exercise and weight loss.

ADA recommends learning your risk and they have a quick online test anyone can take atdiabetes.org/risk-test. People also can ask their doctor about the A1C test, a blood test that can help identify prediabetes or diagnose either Type 1 or Type 2 diabetes.

Impact on everyday life: Learn how Hillary Coleman, a 28-year-old Lansing resident, manages herType I diabetes.

Contact reporter Megan Banta at (517) 377-1261 or mbanta@lsj.com. Follow her on Twitter @MeganBanta_1.

Read the rest here:
Which chronic health issues plague Greater Lansing? Read the list, learn how to beat them - Lansing State Journal

A large attendance from across the midlands turned out last Wednesday, November 6, for an information evening in Athlone about ankylosing spondylitis (AS).

The inflammatory arthritis affects 4,000-6,000 people in Ireland and is most frequently diagnosed in young men.

The talk by Dr Killian ORourke, consultant rheumatologist at the Midlands Regional Hospital, Tullamore, was part of an awareness campaign about the condition organised by Arthritis Ireland.

Dr ORourke outlined that some of the early signs and symptoms of the condition include pain and stiffness in the lower back and buttocks; early morning stiffness; fatigue and poor form; pain and tenderness in the ribs, shoulder blades, hips, thighs and heels; weight loss; fever; mild to moderate anaemia; inflammation of the bowel; and iritis or uveitis.

As ankylosing spondylitis advances, it can affect a persons ability to work. It is estimated that a third of people with AS may be unable to work at all. Around one in six may need to make changes to their working life in order to continue working.

While its not yet known what causes ankylosing spondylitis, there can be a genetic element. However, the condition isnt passed directly from a parent to their children.

Head of communications and advocacy at Arthritis Ireland, Brian Lynch, said: When people are informed about their condition, they are better able to manage the day-to-challenge of living with it. Since ankylosing spondylitis affects people when they are in the prime of their lives, it can be hugely disruptive in terms of their education, careers, relationships, past times.

Our work as a patient organisation is about educating people so that they are aware of symptoms and can take early action. Equally, it is about helping people regain control of their lives through education and support, Lynch said.

Living with Ankylosing Spondylitis is supported by Novartis.

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Offaly doctor speaks at national arthritis event - Photo 1 of 2 - Offaly Express

Danielle C Fair,1 Martha Rodriguez,2 Andrea M Knight,3 Tamar B Rubinstein4

1Division of Pediatric Rheumatology, Medical College of Wisconsin: Childrens Hospital of Wisconsin, Milwaukee, WI, USA; 2Division of Pediatric Rheumatology, Indiana University School of Medicine, Indianapolis, IN, USA; 3Division of Pediatric Rheumatology, Hospital for Sick Children, Toronto, ON, Canada; 4Division of Pediatric Rheumatology, Albert Einstein College of Medicine: Childrens Hospital at Montefiore, Bronx, NY, USA

Correspondence: Danielle C FairMCW Pediatric Rheumatology, Childrens Corporate Center, 999 N 92 nd St., Suite C465, Wauwatosa, WI 53226, USATel +1 414-266-2036Fax +1 414-266-6695Email dfair@mcw.edu

Abstract: Depression and anxiety are prevalent in children with rheumatologic diseases, including juvenile idiopathic arthritis (JIA). However, prevalence rates and the relationship with disease outcomes, including quality of life are conflicting in the early literature. To review the current literature, determine gaps in our knowledge, and identify areas in need of further investigation, we conducted a systematic review of studies examining depression and anxiety symptoms among children with JIA and the impact these symptoms may have on disease outcomes and quality of life. Six electronic databases were searched up until January 2019. Of 799 potential articles, 60 articles were included with the main focus on 28 articles from 2009 to 2019, to concentrate on the most current evidence. We found that JIA patients experience symptoms of depression and anxiety similar to other childhood chronic diseases and at higher rates than in healthy children. Patients who experience these symptoms have worse quality of life, with some evidence pointing to depression and anxiety symptoms having a greater impact on quality of life than other disease features, such as active joint count. Family members of JIA patients experience high rates of anxiety and depression symptoms which may impact their childs mental health and pain symptoms related to JIA. Conflicting reports of associations between depression/anxiety symptoms and disease features/disease outcomes and a paucity of longitudinal studies investigating the impact of treatment on mental health symptoms indicate areas in need of further research to effectively identify patients at greatest risk of depression and anxiety and to better understand how to treat and prevent these symptoms in youth with JIA. Family mental health should also be considered in investigations concerning mental health and disease outcomes of children with JIA.

Keywords: pediatric rheumatology, mental health, mood disorder, arthritis, autoimmune disease

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

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Depression And Anxiety In Patients With Juvenile Idiopathic Arthritis: | OARRR - Dove Medical Press

November 07, 2019 -Telehealth services are proving equal to in-person care in studies all across the country, but only if all the stars are aligned.

The latest example comes from Alaska, where a program launched for people living with rheumatoid arthritis found that virtual visits compared just as favorably to in-person care, as long as both provider and patient were familiar with telehealth.

The telehealth service also proved popular with patients who deal with frequent flare-ups, as it offered them a more convenient means of getting in front of a care provider.

When offered as an option for rheumatology care, video telemedicine was more likely to be used by RA patients with higher disease activity, more positive perceptions of telemedicine, and whose physicians used telemedicine more often, the researchers, led by Elizabeth D. Ferucci, of Community Health Services and the Alaska Native Tribal Health Consortium, wrote in the August edition of Arthritis Care & Research.

The intimation is that telehealth has to be familiar in order to be embraced. And that means more people providers and patients have to be introduced to telehealth in order to become familiar with its benefits.

For their study, Ferucci and her colleagues gathered data from 122 Alaskans being treated for RA in the Alaska Tribal Health System between August of 2016 and March of 2018. The participants were given a choice of in-person care at the Alaska Native Medical Center in Anchorage (with an out-of-state rheumatologist participating via video) or virtual visits.

According to the researchers, those using virtual visits met more often with their care providers. In addition, they had a more positive perception of telehealth, and they were seeing a rheumatologist who used telemedicine more frequently.

Also, both groups indicated they preferred to see a specialist in person for follow-up care 61 percent of those who used telehealth and 74 percent of those who visited the hospital. But those within the telehealth group also said their virtual care experience was just as good as in-person care.

The study points out that telehealth is embraced by those who have already tried it, but isnt high on the to-do list for those who havent used it yet. That falls in line with the many surveys that find telehealth to be popular in concept but not in use.

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In Alaska, Telehealth is Popular With Those Who Have Already Used It - mHealthIntelligence.com

The market research study titled Global Rheumatoid Arthritis and Lupus Treatments Market Growth (Status and Outlook) 2019-2024specialized in current industry updates covers exclusive and analytical data through the span of seven years between 2019-2024. The research report has examined global market trends with recently obtainable data relevant to the amount of both market businesses and their market share. The report studies how the challenges, risks, current approaches, and social problems could limit the market. It serves an excellent guide with the help of bar-graphs, pie charts, product figures, tables. It will offer an exact outlook of the industry for interested users.

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Geographically, this report is divided into many key regions, with production, consumption, revenue (million USD), and market share in these regions, from 2019 to 2024 (forecast), covering:Americas (United States, Canada, Mexico, Brazil), APAC (China, Japan, Korea, Southeast Asia, India, Australia), Europe (Germany, France, UK, Italy, Russia, Spain), Middle East & Africa ( Egypt, South Africa, Israel, Turkey, GCC Countries).

This portion appraises the market based on top vendors, their organization detailing, volume, areas, supply-demand scheme, and development trends. Top players are: AbbVie, Amgen, Bayer, Biogen Idec, Roche, Johnson and Johnson, Merck, Mitsubishi Tanabe Pharma, Novartis, Pfizer.

Split by type, this report focuses on consumption, market share and growth rate in each application can be divided into Rheumatoid Arthritis Treatments, Lupus Treatments.

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Important Points Featured In This Report Are:

Manufacturing Analysis Rheumatoid Arthritis and Lupus Treatments market synopsis is given concerning the top countries, types, and applications. In addition, the section also covers price analysis of varied market vital players.

Revenue and Sales Evaluation Both, earnings and sales are studied for different elements of this market. Here, price plays an important role in the sales creation that can be analyzed for several regions.

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Competition In this section, many global industry-leading players have been studied based on their company profile, product portfolio, capacity, price, price, and earnings.

In conclusion, the report gives the analysis of the parent market supported key players, present, past and artistic movement information which will guide industry competitors. Additionally, a point-to-point notion of some important criterions like item value supply & distribution channels, profit and loss figures, production capability, and others are also given in this report. It will act as a profitable platform for users who aims to grasp each and every single opportunity of the Rheumatoid Arthritis and Lupus Treatments.

Customization of the Report:This report can be customized to meet the clients requirements. Please connect with our sales team (sales@fiormarkets.com), who will ensure that you get a report that suits your needs.

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Rheumatoid Arthritis and Lupus Treatments Market 2019 Global Industry Size, Share, Comprehensive Study, Trends, Demand Status, Forecast to 2024 -...

Dashing through the snow at 25 miles an hour,Heather Huson97 got her first thrill as a musher at age 7. From then on, she was hooked on dog sledding, and raced competitively for almost 30 years throughout North America.

By the end of her racing days, she had competed twice in sled dog racings equivalent to the Olympics the International Federation of Sleddog Sports World Championships. And she ended her racing career with a bang, winning an extremely competitive six-dog class race at the 2004 Tok Race of Champions in Tok, Alaska.

Heather Huson shares time with a sled dog at the Baker Institute.

Now an assistant professor of animal science, Huson is co-leader of a $4.2 million project studying close to 100 Alaskan sled dogs between the ages of 8 and 13, former athletes past their glory days. The study, which began in 2018, is a quest for one of the holy grails of medicine: how to slow aging.

This project allows me to work with sled dogs again, but now Im studying their aging and health, said Huson, a molecular geneticist in the College of Agriculture and Life Sciences.

Huson and co-leaderDr. John Loftus, assistant professor of small animal medicine in the College of Veterinary Medicine, are trying todetermine whether a drug that inhibits an enzyme called reverse transcriptase can mitigate aging and extend life in older dogs. Private donations fund the project through the Vaika Foundation, a nonprofit group of scientists and veterinarianson a mission to extend the health and life span of domestic animals.

The project will serve as a proof of principle for whether reverse transcriptase inhibitors could be an elixir. If confirmed, new finely tuned drugs could be developed for both dogs and humans.

While we love dogs, and we care about extending the life span of dogs for its own right, this is also a really good model for people, hopefully, in the future, Loftus said.

Genetics of aging

Other researchers, including project collaborators at the Roswell Park Comprehensive Cancer Center in Buffalo, New York, have found evidence in mice that reverse transcriptase inhibitors suppress tumors and extend life span.

The next step was to go to a model organism thats more closely related to humans in similar environments, and more similar to the types of diseases that people get, Huson said.

While we love dogs, and we care about extending the life span of dogs for its own right, this is also a really good model for people, hopefully, in the future.

John Loftus

In mammals, viruses that infected distant ancestors left behind some of their DNA, which are called genetic elements.

As we age, were finding these normally dormant DNA elements get turned on and then behave like viruses in the body, said Loftus, a veterinarian and researcherwho leads the immune system analysis on this project.When DNA elements get turned on, they can encode [for] a number of proteins, and reverse transcriptase is one of them.

In turn, reverse transcriptase plays a role in duplicating more of these genetic elements, which become randomly inserted in the genome and can lead to mutations and cancer.

And since these elements act like viruses in cells, they also trigger an immune response, which creates inflammation.

The federally approved drug being tested in the sled dog project is commonly prescribed to people for viral infections.

Our approach is going to be to give the dogs a reverse transcriptase inhibitor to turn the transcriptase off, Loftus said, and hopefully reduce inflammation, reduce the incidence of cancer and other diseases related to mutations and DNA damage, and ideally increase life span.

Heather Huson watches as a sled dog runs during play time in a fenced field at the Baker Institute for Animal Research at Cornell.

Why Alaskan sled dogs?

Dogs offer many advantages over mice as research subjects. They share with humans similar lifestyles and aging-related diseases like cancer and cognitive dysfunction, and serve as a model for studying Alzheimers disease.

Originally, the researchers proposed to study pet dogs. But maintaining a uniform diet for all participants and trusting owners to administer the drug consistently proved too unreliable.

We had the idea instead to create a colony of dogs we had control over, Huson said. They realized athletic dogs were housed in groups, in kennels, and as they age, owners kept their best dogs and often sold the rest to hobbyists or as pets.

So that gave us an avenue for how we could get these dogs, Huson said.

For her doctorate, Huson studied the genetics and selective breeding in Alaskan sled dogs at the University of Alaska, Fairbanks. She discovered that sled dogs are a genetically distinct breed. They have undergone intense selection for such traits as athleticism, but at the same time are subject to an open breeding scheme,with a diverse gene pool that makes for fewer genetic issues and diseases than pure breeds.

John Loftus greets a sled dog at the Baker Institute for Animal Research.

Yet they create a unique population that is still homogenous that we can study and say, this response to the drug is potentially related to the drug and not because its a poodle versus a beagle, Huson said.

In late May 2018, Huson and Loftus began acquiring dogs, which they kenneled at the Baker Institute for Animal Research at Cornell. Huson traveled twice to Alaska, and she and others, including students, picked up dogs from Canada, Michigan, Minnesota, Oregon, Washington and other states.

Locating dogs and bringing them to the Baker Institute required countless cross-country trips on planes and by vehicle. By September 2018, they had 102 dogs for the study. In March 2019, the researchers collected the firstbaseline data.

Testing aging over time

To test the drugs effectiveness, Huson and Loftus have been quantifying aging in the dogs every six months through three avenues immune function, behavior and physical condition. All the tests are noninvasive or minimally invasive.

They are testing two types of immune responses: adaptive responses that react quickly to infections; and innate responses where the immune system recognizes and delivers specific antibodies to fight a pathogen that previously entered the body. They are also checking blood for increases in markers for inflammation.

Four cognitive dysfunction behavioral tests involve an empty behavioral testing room with a video camera to record lone dogs as they encounter such things as a stranger sitting still in a chair, a familiar or novel toy, or a mirror.

Heather Huson racing in an Alaska Dog Mushers Association Challenge Series race in 2005 at the Jeff Studdard Sled Dog Race Track in Fairbanks, Alaska.

For physical tests, dogs are fitted with a racing harness and are trained to run on a treadmill with heart rate and electrocardiogram monitors. The treadmill has special sensors under the belt to record the pressure of each footfall, to detect limping that could come with arthritis. Another test times dogs as they pull one-and-a-half times their weight a distance of 40 yards using a pull harness.

It will take years to gather enough data for the researchers to make a definitive statement about the drugs effects. But funds have already been allotted to provide the dogs with a high quality of life until they die of natural causes.

Twice a day the dogs go outside for play time. As soon as the kennel doors open, the dogs, tongues flapping, scurry excitedly down a long hallway toward the light of an open door that leads to three separate fenced fields where they play, run, sniff the grass and greet the student volunteers outside.

It reminds Huson of her childhood, when her family owned as many as 50 sled dogs.

I used to train dogs to run all the time, Huson said. Now were training them to run in a slightly different scenario. Its fun and rewarding. And, its therapy for us.

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Sled dogs lead the way in quest to slow aging - Cornell Chronicle

As concerns over antibiotic resistance grow, equine veterinarians look for ways to treat wounds without reaching for these powerful drugs. At the 2019 British Equine Veterinary Association Congress, held Sept. 11-14 in Birmingham, U.K., Dean Hendrickson, DVM, Dipl. ACVS, described ways to do just this, ranging from debridement to stem cell therapy.Debridement

The best way to deal with bacteria is to get rid of them, said Hendrickson, a professor in the Clinical Sciences Department at Colorado State Universitys Veterinary Teaching Hospital, in Fort Collins.

We have a tendency in veterinary medicine to want to kill the bacteria in situ, but Im going to encourage you to remove them and throw them away and dont let the patient have to deal with them at all, he advised the audience.

Veterinarians can remove bacteria through debridement (removing the affected tissue), of which there are several types:

Autolytic debridement. This process uses the bodys own enzymes and moisture to liquefy and remove necrotic (dead) tissue. Hendrickson said its the most selective way to remove bacteria and dead cells while leaving healthy cells.

All youre doing is leaving the healthy wound exudate (liquid the body produces in response to tissue damage) in contact with the wound bed to accomplish this, he said. The normal white blood cells and proteolytic enzymes that occur in wound exudate are your best friends with regard to removing small doses of bacteria and small amounts of necrotic tissue.

To achieve autolytic debridement, you must keep the wound environment moist (but not soupy), which you can do using dressings. If the wound has a lot of necrotic tissue, however, then youll need to use a more aggressive form of debridement, said Hendrickson.

Biological debridement. This method involves using an organism, such as maggots, to remove dead tissue.

It still amazes me how effective maggot debridement is and how rarely we actually use it, said Hendrickson. When a horse comes into the clinic with maggots in its wound, he said people tend to get squeamish and try to remove them, but these guys are doing their jobtheyre getting rid of the necrotic tissue (and pathogenic bacteria). Theres a lot of value to that, and its very rapid and selective.

Enzymatic (chemical) debridement. With this method, veterinarians apply manufactured proteolytic enzymes to the wound to break down devitalized tissue.

This is another great way (to debride wounds), but we dont tend to use it very frequently in veterinary medicine because of the cost of the enzymes, said Hendrickson. Studies have found it to be very effective at reducing bacteria but not as good as autolytic debridement. So the body in and of itself is the best way to go if you have low levels of bacteria.

Mechanical debridement. This technique involves using force to remove tissue. Examples include wet-to-dry dressings and wound irrigation. Its something we do really well in veterinary medicine, almost to a fault, he explained. We scrub, we lavage, and we cause a significant amount of trauma to the wound bed.

On the plus side, mechanical debridement is inexpensive and effective. The downside? It can cause shear stresses to the underlying granulation (scar) tissue, which can lead to further problems down the road, Hendrickson said.

He recommended using the minimal amount of force and pressure necessary.

Sharp debridement. This method involves using tools such as scalpels or curettes to physically remove tissue. Its the most aggressive form of debridement and the most effective way to remove large amounts of bacteria and necrotic tissue, said Hendrickson.

Theres a lot of value to wound debridementthat should be your first step toward reducing bacteria numbers and necrotic tissue, he said. We should not be bathing them with local or systemic antimicrobials. Remove the infected tissue thats there.

Veterinarians can use a variety of debridement dressings to help remove bacteria and dead tissue. Ones Hendrickson said are useful include:

Hypertonic saline. This solution comprises 20% saline, which you can buy commercially or make yourself using salt and water.

The idea is the hypertonic environment created by this saline will kill the bacteria because theyre unable to deal with that environment, and it will also remove the necrotic tissue, Hendrickson said.

While these are highly effective, he said theyre less selective than autolytic, biologic, or enzymatic dressings. He also cautioned against overusing them, because they have the potential to be toxic.

Honey. This substance is both hypertonic and antimicrobial. It can help heal burns, for instance, faster and with fewer adverse effects than other dressings, said Hendrickson.

Researchers have performed a variety of studies confirming the efficacy of honeys such as manuka honey. Further, said Hendrickson, theres some recent evidence out there that shows that local raw honey is more effective at killing local bacteria than medical grade honey.

Polyhexanides (e.g., polyhexamethylene biguanide, or PHMB). Certain sterile antimicrobial dressings are very effective at killing bacteria, even multidrug-resistant varieties. Theyre not antiseptics and should not be confused with them, said Hendrickson.

He then provided the audience with smart antibiotic use tips for when they do need these drugs to combat infection, starting with a sensitivity culture to identify the specific bacteria.

Whether its systemic or local antibiotic therapy, do a culture to know whats happening, then always use the simplest, lowest level of antibiotic possible, he said. While your first dressing might require using an antibiotic you cant pick because you dont know whats there, at least try to get a culture so you can make the decision later on.

Only use antibiotics for short periodstwo weeks or less, he said.

As for topical antibiotics, he recommended using silver dressings or, preferably, triple antibiotic, which hasnt seen much resistance over the decades its been in use.

Hendrickson also reviewed promising studies looking at mesenchymal (embryonic connective tissue) stem cell use in wound treatment: The one place there is evidence for stem cells is in the reduction of bacteria numbers in wounds.

There are lots of ways to reduce bioburden (number of bacteria) in wounds, said Hendrickson. I think wound debridement is the best way to accomplish that. Get rid of the necrotic tissue, and dont use antiseptics in your wounds, because they just create more necrosis, thereby encouraging the number of bacteria forming.

And if you do have to resort to antibiotic administration, choose your antimicrobials well, and use them sparingly, he said.

Read more:
Managing Horse Wounds Without Antibiotics - TheHorse.com

Gene therapy has traditionally been applied to well-understood diseases where a single genetic mutation was to blame. A new generation of technology is expanding the potential of gene therapy to treat conditions that were previously unreachable.

Since the first gene therapy clinical trials in the 1990s, the technology has made its way into the market for conditions ranging from blindness to cancer.

Gene therapy has the potential to fix any genetic mutation causing disease by inserting a new copy of the faulty gene. However, its reach has historically been limited.

Weve been constrained with the things we can do with gene therapy, said Dmitry Kuzmin, Managing Partner at 4BIO Capital, a London-based VC that specifically invests in advanced therapies. If you look across the successes in gene therapy in the last five years, most of these were in diseases that are pretty straightforward from the engineering perspective.

Technical limitations have meant that gene therapy has been restricted to rare diseases caused by a single genetic mutation, as well as to certain areas of the body, such as the eye and the liver.

According to Kuzmin, there have been so far three generations of gene therapy technology. Generation one would be classic single-gene replacement, such as Luxturna, a gene therapy to fix a specific genetic mutation causing blindness. Generation two would consist of using gene therapy to introduce new functions. An example is Kymriah, where immune cells are equipped with a molecule that helps them hunt down cancer cells.

The third generation is the one that could hold the key to unlocking the full potential of gene therapy. It englobes several technologies that can be used to introduce a new drug target into the patient, making it possible to turn the therapy on and off as well as to tune its intensity.

As the first two generations get optimized and the third generation enters the clinic, we are now expanding our reach into areas that have been previously rather inaccessible, Kuzmin told me. One of them is the brain.

Treating the brain has long been a huge challenge for medicine. Take epilepsy, for example.

Epilepsy affects 1% of the whole population and about 30% of people with seizures of epilepsy continue to have seizures despite medication, said Dimitry Kullmann, Professor at University College London. Theres a paradox. We have a good understanding of the mechanisms behind epilepsy, but were unable to suppress seizures in a significant proportion of people with epilepsy.

The reason is that the molecules that we use for drugs dont target the epileptic zone of the brain; they bathe the entire body with medication, Kullmann told me. These drugs dont differentiate between neurons and synapses that derive the seizures, and those parts of the brain that are responsible for memory, sensory functions, motor functions and balance.

Gene therapy could provide a solution for this problem. Kullmanns group has been researching this approach for years and is now getting ready to start the first clinical trial in humans within a year.

A gene therapy can be directly injected in the area of the brain causing seizures. Furthermore, using DNA sequences called promoters, it is possible to restrict the effect of gene therapy to specific neurons within that area. In the case of epilepsy, gene therapy can be used to decrease the activity of only excitatory neurons, which cause epileptic seizures when they are overactive.

Another approach that Kullmans group is testing is chemogenetics. The idea here is to use gene therapy to put a specific receptor into the neurons, explained Kullmann. This receptor is designed to respond to a drug that, when given to the patient, decreases the activity of the neuron to suppress seizures.

The advantage is that you can switch on and off the therapeutic effect on demand by just giving, or not giving the drug, Kullmann said. This approach can thus make gene therapy more precise, being able to tune it to the specific needs of each patient. In addition, it reduces the big challenge of getting the dose right in a one-off treatment.

Ultimately, this technology could allow scientists to target a wide range of conditions that come under the umbrella of epilepsy, rather than just a specific form of the condition caused by a genetic mutation.

The approach could be extended to other conditions involving the brain, such as Parkinsons, ALS and pain. However, this kind of research is still at an early stage and it will take a while until its potential is proven in humans.

Blindness has been a major target of gene therapy because of the fact that the eye is an ideal target for this technology. The activity of the immune system is suppressed in the eye, minimizing the chances of rejection. In addition, unlike other cells in the body, those involved in vision are not renewed over time, being able to retain the injected DNA for years.

However, there are hundreds of genetic mutations that can cause blindness. With the classical gene therapy approach, a different therapy would have to be developed from scratch for each mutation. While some companies are doing just this for the most common mutations causing blindness, many other less frequent mutations are being left behind.

Others are turning to new generations of gene therapy technology. We figured out that it would be very, very difficult to use the classical gene therapy approach in each individual mutation, said Bernard Gilly, CEO of GenSight, a Parisian biotech developing gene therapies for blindness.

While the companys leading programs follow this classical approach, the company has also started clinical trials using a technology called optogenetics. Following a similar principle to gene therapy, optogenetics consists of introducing a protein that reacts to light into a cell.

GenSight is using optogenetics to develop a single therapy for the treatment of retinitis pigmentosa. This genetic condition can be caused by mutations in any of over 200 genes and results in progressive vision loss in children due to the degeneration of photoreceptor cells that perceive light and send signals to the brain.

With optogenetics, it would be possible to transfer the lost photoreceptor function to the cells in the retina that are responsible for relaying visual information to the brain. Using specialized goggles, the images captured by a camera are transformed into light patterns that stimulate these cells in the precise way needed for the brain to form images.

The company is currently testing this approach in clinical trials. We believe that this approach will allow us to restore vision in those patients who became blind because of retinitis pigmentosa, Gilly told me.

Optogenetics would not work a miracle, but it might be able to give people back the ability to navigate an unknown environment with a certain level of autonomy. Recognizing faces is a more challenging goal; although reading is not yet on the horizon, according to Gilly.

Still, the potential of optogenetics to address multiple genetic mutations with a single treatment might be revolutionary. As long as the neurons responsible for sending light signals to the brain are intact, this approach could be extended to other forms of blindness. In addition, conditions affecting the brain such as epilepsy, Parkinsons or ALS could be treated with this approach by introducing an implant to shine light on the target neurons.

However, approaches applying optogenetics to the brain are still further down the line. While optogenetics technology has been around for over 20 years, its application in humans is still very limited and in the early stages of research.

Chemogenetics and optogenetics are just two out of a wave of new technologies addressing the historical limitations of gene therapy. Other approaches are in development, such as using thermogenetics, which consists of introducing proteins that are activated by the heat created by infrared light.

With a growing range of tools available, it is becoming easier than ever for scientists to develop gene therapies that can address the specific challenges of different conditions affecting areas of the body. Traditionally, locations such as the heart, the lungs or the pancreas have been particularly difficult to target with gene therapy. That might soon stop being the case.

As we go forward, were interested in taking gene therapy out of this little box and trying to use all the knowledge we have to benefit patients in larger indications, said Kuzmin.

As gene therapy expands into more mainstream conditions, it could take precision medicine to a whole new level and help address the big variability that is often seen across patients with the same diagnosis.

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How Gene Therapy Is Evolving to Tackle Complex... - Labiotech.eu

Across 2019, Vertex has struck deals intended to yield a new generation of breakthrough medicines.

In June, Vertex agreed to pay $245m (220m) upfront to acquire Exonics Therapeutics for its gene editing technology and pipeline of programs targeting diseases including Duchenne muscular dystrophy (DMD). Months later, Vertex put up another $950m to buy Semma Therapeutics and its cell therapy treatment for type I diabetes.

The acquisitions moved Vertex, which started out in small molecules, into new areas, and building out capabilities in those areas will cost money.

In recent years, Vertex has grown its annual operating expenses by 10% to 14%. Talking on a recent quarterly results conference call, Vertex CFO Charles Wagner warned investors to expect costs to rise faster in 2020.

Wagner said, Our current expectation is that the rate of growth will be somewhat higher in 2020 as we invest in research and preclinical manufacturing for selling genetic therapies in support of our programs in type I diabetes, DMD and other diseases.

The move into type I diabetes also takes Vertex into territory that, to some observers, looks different than the areas the company has targeted historically.

Asked by an analyst about the shift in focus, Vertex CEO Jeff Leiden downplayed the differences, noting that type I diabetes is treated in the US in a relatively small number ofcenters that can be targeted by a speciality sales force.

Researchers have achieved positive, long-term outcomes by transplanting cadaveric islets into patients but two barriers have stopped companies from industrialising that approach.

Firstly, there are too few cadaveric islets to treat all type I diabetics. Secondly, immunosuppression is needed to stop patients from rejecting the transplanted cells.

Semma is trying to tackle the problems by differentiating stem cells and using a device to protect them from the immune system. Vertex thinks these technologies are the breakthroughs the field needs to industrialize the concept.

Leiden said, We were watching companies who are addressing those two problems for the last two, three years. And over the last six to eight months, we were convinced that Semma has actually solved both of those problems.

Vertex reached that conclusion on the strength of preclinical data. Now, Vertex is set to invest to find out whether the idea works in the clinic.

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Vertex invests in gene therapy manufacturing - BioPharma-Reporter.com

As people age, they tend to develop diseases such as heart failure, kidney failure, diabetes, and obesity, and the presence of any one disease increases the risk of developing others. Traditional drug treatments, however, each target one condition. That means patients often have to take multiple medications, increasing both the risk of negative side effects and the likelihood of forgetting one.

New research from the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard Medical School (HMS) suggests that it may be possible someday to tend to multiple ailments with one treatment.

In the Wyss study, a single administration of an adeno-associated virus (AAV)-based gene therapy, which delivered combinations of three longevity-associated genes to mice, dramatically improved or completely reversed multiple age-related diseases, suggesting that a systems-level approach to treating such diseases could improve overall health and lifespan. The research is reported in PNAS.

The results we saw were stunning and suggest that holistically addressing aging via gene therapy could be more effective than the piecemeal approach that currently exists, said first author Noah Davidsohn, a former research scientist at the Wyss Institute and HMS who is now chief technology officer of Rejuvenate Bio. Everyone wants to stay as healthy as possible for as long as possible, and this study is a first step toward reducing the suffering caused by debilitating diseases.

The study was conducted in the lab of Wyss core faculty member George Church as part of Davidsohns postdoctoral research into the genetics of aging. Davidsohn, Church, and their co-authors homed in on three genes that had been shown to confer increased health and lifespan benefits in mice that were genetically engineered to overexpress them: FGF21, sTGFR2, and Klotho. They hypothesized that providing extra copies of those genes to nonengineered mice via gene therapy would similarly combat age-related diseases and bring health benefits.

The team created separate gene therapy constructs for each gene using the AAV8 serotype as a delivery vehicle, and injected them into mouse models of obesity, Type 2 diabetes, heart failure, and renal failure both individually and in combination with the other genes to see whether there was a positive synergistic effect.

FGF21 caused complete reversal of weight gain and Type 2 diabetes in obese, diabetic mice following a single gene therapy administration, and its combination with sTGFR2 reduced kidney atrophy by 75 percent in mice with renal fibrosis. Heart function in mice with heart failure improved by 58 percent when they were given sTGFR2 alone or in combination with either of the other two genes, showing that a combined therapeutic treatment of FGF21 and sTGFR2 could successfully treat all four age-related conditions, therefore improving health and survival. Administering all three genes together resulted in slightly worse outcomes, likely from an adverse interaction between FGF21 and Klotho, which remains to be studied.

Importantly, the injected genes remained separate from the animals native genomes, did not modify their DNA, and could not be passed to future generations or between living animals.

Achieving these results in nontransgenic mice is a major step toward being able to develop this treatment into a therapy, and co-administering multiple disease-addressing genes could help alleviate the immune issues that could arise from the alternative of delivering multiple, separate gene therapies for each disease, said Church, who is also a professor of genetics at HMS and professor of health sciences and technology at Harvard and MIT. This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself.

Church, Davidsohn, and co-author Daniel Oliver are co-founders of Rejuvenate Bio, a biotechnology company that is pursuing gene-therapy treatments for dogs. Each holds equity in Rejuvenate Bio.

The finding that targeting one or two key genes has therapeutic effects in multiple diseases makes enormous sense from the perspective of pathophysiology, but this is not how drugs are normally developed. This ability to tackle several age-related diseases at once using gene therapy offers a potential path to make aging a more manageable and less debilitating process, said Wyss Founding Director Donald Ingber, who is also the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Childrens Hospital, as well as professor of bioengineering at Harvards John A. Paulson School of Engineering and Applied Sciences.

Reference: Davidsohn et al. 2019.A single combination gene therapy treats multiple age-related diseases. PNAS.https://doi.org/10.1073/pnas.1910073116.

This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Combination Gene Therapy Could Treat Multiple Age-related Diseases - Technology Networks

Harvard synthetic biology pioneer George Church generated some buzz last year when he co-founded Rejuvenate Bio with the goal of reversing aging with gene therapy. Now, he and his co-founders say they have compelling early evidence in mice that they can use the technology to reverse multiple age-related diseases at once.

The researchers gave the mice three genes associated with longevity, either alone or in various combinations. The genes were FGF21, sTGF2betaR and alpha-Klotho. In previous experiments, they had shown that mice genetically engineered to overexpress the genes experienced benefits in both their health and life spans.

This time, they used mice that were not genetically engineered but rather models of obesity, Type 2 diabetes, heart failure and kidney failure. They wanted to prove their hypothesis that giving the mice extra copies of the genes might confer similar health benefits. They found that some combinations did improve or reverse symptoms, they reported in the journal Proceedings of the National Academy of Sciences.

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The Harvard team discovered that a combination of FGF21 and sTGF2betaRcould treat all four diseases. FGF21 administered on its own reversed weight gain and Type 2 diabetes, and, when it was combined with sTGF2betaR in mouse models of kidney failure, it lowered kidney atrophy by 75%.

Administering all three genes together turned out to be an unsuccessful strategy, however. Mice that received that combination had worse outcomes than the other animals did, the team reported. The researchers believe there may have been an adverse reaction between FGF21 and alpha-Klotho, but they said further experiments would need to be designed to confirm that.

RELATED: George Church founds cryptocurrency-fueled genomics firm

Rejuvenate Bio was launched from Churchs lab at Harvard Medical School and the Wyss Institute for Biologically Inspired Engineering in 2017 but is still largely in stealth mode. It generated some attention last year, after it started reaching out to dog owners with the opportunity to enroll their pets in a trial of a gene therapy to treat mitral valve disease. The heart condition affects some breeds in outsized numbers, including Cavalier King Charles spaniels.

The potential benefits of the three genes Churchs team investigated for the newly published study are well known. FGF21, for one, has been shown to play a beneficial role in insulin resistance and fat metabolism. And last year, researchers partially funded by diabetes drug maker Novo Nordisk discovered that a variant in the gene is present in some people with naturally low levels of body fat.

Last year, Yale researchers discovered that beta-Klotho promotes weight loss, glucose metabolism and insulin sensitivity by binding to FGF21. And a separate team led by New York University published their discovery that alpha-Klotho facilitates FGF23 signaling, which in turn modulates the aging process.

Rejuvenate Bios Church said in a statement that a one-time gene therapy to address multiple age-related diseases could offer several benefits for patients and that the mouse trial was a major step toward the companys efforts to develop gene therapies for human use.

"This research marks a milestone in being able to effectively treat the many diseases associated with aging, and perhaps could lead to a means of addressing aging itself," Church said.

View original post here:
Gene therapy to fend off aging? Buzzy Harvard startup Rejuvenate Bio says it works in mice - FierceBiotech

Ger Brophy, PhDExecutive Vice PresidentBiopharma ProductionAvantor

Genuine progress is being made in the long-standing battle to effectively treat and control disease. The National Cancer Institute projects that nearly five million more U.S. citizens are expected to survive cancer in 2026 than in 20161. Therapeutic tools like next-generation sequencing and advances in immunotherapy are just two ways that fundamental scientific breakthroughs and innovative thinking are moving the potential for cancer treatment forward.

One of the most revolutionary advances in this new era is cell and gene therapy. At its most basic definition, gene therapy (also called human gene transfer) is the therapeutic delivery of nucleic acid into a patients cells as a drug to treat disease. According to The Journal of Gene Medicine, just over 2,700 gene therapy clinical trials have been undertaken in 38 countries around the world as of 20182.

These clinical trials demonstrate that the recent attention being paid to gene and cell therapy is not just hype. Although initial approvals have been for relatively small patient groups, the significant pipeline of gene therapy studies for diseases such as hemophilia and various forms of blindness will significantly expand the impact of these treatments. Its exciting to see the number of trials grow, especially when one considers this technologys ability to impact patients lives.

Its true that the number of patients receiving treatment is relatively small compared to other therapeutic regimens, but thats to be expected. Many of the biopharmaceutical researchers and manufacturers started with smaller, defined patient populations as, for example, those with relapsed pediatric refractory acute lymphoblastic leukemia. In part, these early efforts were directed at this type of cancer because the researchers wanted to deal with small populations that they understood well and, in many cases, had few or no other options for treatments.

The success of these initial cell therapy efforts has led to broader programs targeting larger populationsstarting with leukemia and now lymphomas. Ultimately, the most challenging opportunity, and the one with the greatest potential for beneficial outcomes, is multiple myeloma. If these patients begin to see benefits from cell and gene therapies, it will justify the incremental approach the industry has been taking.

The genuine, almost unprecedented potential for cell and gene therapy cannot be understated. For the first time, people are talking about curing these ruthless, relentless diseases. In a way never before possible, were taking control of and harnessing the patients own immune system to fight these cancers. At the recent Alliance for Regenerative Medicine Cell and Gene Therapy on the Mesa meeting, the significant response and survival rates from patients with Diffuse Large B-Cell lymphoma, Acute Lymphoblastic Leukemia, Non-Hodgkins Lymphoma, and Spinal Muscular Atrophy were noted and discussed.

The game changer here is that cell and gene therapy use the bodys own systems, either the cellular immune system or the ability to repair and replace defective or missing genes. CAR-T cell therapy is arguably among the most personalized medicines one can consider. The patients own T cells are extracted, modified, activated, expanded, purified and returned to the patient.

The promise of personalized medicine has been held out for a long time, and now were actually beginning to see real, tangible effects from decades of research into the genetics of the human genome and cancer, giving us an understanding of how the disease develops and how patients respond.

Significant growth is underway in the size and sophistication of companies and organizations entering the cell and gene therapy markets. Many of the early movers in cell and gene therapy were small biotech startups. In some cases, their treatments were supported by major hospital centers.

Now, weve seen a significant interest from the major biopharma industry. Novartis, in particular, has been active and led the way in securing approval for Kymriah. Novartiss focus in this area continued with the acquisition of AveXis and securing the approval of Zolgensma to treat spinal muscular atrophy (SMA). Since last year, weve also seen several important acquisitions by Gilead snatching Kite Pharma, Roche adding Spark Therapeutics, Bristol-Myers Squibb acquiring Celgene, and other companies in China driving large strategic partnerships with major biopharma companies. As companies of this size get involved, the hope is that they will leverage their increased breadth and depth to develop new labels, new trials and find ways to manufacture these therapies at scale.

Scalability and manufacturability are the two, closely-related challenges the industry faces, especially if cell and gene therapies are to fulfill their clinical potential. At first, the questions to be answered appear quite daunting: Can we manufacture cell and gene therapies at scale? If we can manufacture these treatments at scale, then can we do so safely? Can we do so at a reasonable cost so the populations that are affected by these diseases can access treatments?

And the problems presented are new. With autologous cell therapy, one must think about drug product in a different way. There is no inventory; the patient is waiting, and the risk/reward balance is different.

One issue is process standardization. With cell therapy, the single biggest point of variability is the patients own cells. And by its very nature, this is specific to the patient and specific to the health of the patient at the time of leukapheresis.

Variables and failure modes must be taken out of the manufacturing process. And innovations in process technology can make a real difference. We can standardize and close production systems so theyre less exposed to failure modes. Processes can be miniaturized to drive cost efficiencies and, perhaps, better clinical outcomes. We can employ better workflow technologies, such as single-use sterile-fluid transfer. Fill/finish requirements will surely be different for cell and viral products and improved excipient technologies will play a large part in better patient experience and response. Different analytical standards will apply, particularly in relation to adventitious agents during cell expansion.

In particular, the numbers around virus production for gene therapy and ex-vivo cell therapy just dont add up. Adherent process and packaging systems are inefficient. Given the high viral titer numbers indicated in recent approvals, it will be difficult to scale these manufacturing operations. Either something must change, or massive manufacturing future capacity will need to be built. In the meantime, there will be significant reliance on CMOs for capacity.

Across the board, improvements in raw material inputs and innovations in manufacturing technology are now required if we are to see the deployment of these therapies economically and at scale.

To address these challenges, cell and gene therapy producers and the supply companies that support them need to develop stronger partnerships. In areas such as cell culture components, production chemicals, single-use technologies, sterile fluid transfer, excipients, and the technology surrounding those process components, there is value to improving collaboration and trying new solutions to address the issues of manufacturability and scale.

We need to better analyze and understand the variability that comes from the research data, even at the early stages of these trials, and use it to correlate with clinical and process outcomes. Taking out manual steps as early as possible is important, as well as creating closed systems using sterile fluid transfer technologies.

One of the most significant challenges is finding solutions around side effects. As we understand how to provide a more efficacious dose, perhaps using less cells, some of the side effects of these drug therapies may improve. Furthermore, we must find scalable ways to address costs which are far too high. Ultimately, these drugs must be developed in a more cost-effective manner. Thats an area where technology providers and suppliers can play a significant role, by closing and automating systems and by understanding the contribution of labor and overhead and possible economies of scale from reducing processes.

There have been encouraging improvements in the way various global regulatory groups have supported gene and cell therapy. To a certain degree, there was a perception of an arms race between different regional bodiesthe U.S., Europe and the UK, China, and Japan and in different ways within different specialties.

More recently, it appears that regulatory bodies have been open and collaborative in acknowledging that cell and gene therapy is different from more mature biopharma cancer treatments. They are willing to put the appropriate regulatory system into place to enable these drugs to get to market and to monitor them going forward.

The U.S. FDAs support on CAR-T technologies is a good example. Regulators are allowing flexibility in the normal hierarchy of how clinical trials are performed, particularly in phase II and III trials, but the companies must still address the FDAs post-marketing comments and safety issues.

Undoubtedly, cell and gene therapies will have a significant role to play in disease treatment, given the personalized and precise nature of the treatments. But this will be against the backdrop of many existing and emerging therapy paradigms.

Both large molecules and small molecules will continue to provide trusted, effective solutions with each type of drug product finding its niche. For example, we have seen recent encouraging news in the area of monoclonal drugs for neurodegenerative diseases. And emerging fields such as nucleic acid based drugs are showing strong potential thanks to improvements in formulation and delivery.

Its worth remembering that monoclonal-based therapies and biopharmaceuticals have really only started to make a significant impact in the last 15 to 20 years. Cell and gene therapies are just emerging and have yet to make a significant market impact. With that consideration, whos to say whats next? Expanded programs in basic research to develop, understand and characterize drug targets; an exciting program of clinical development and improvements in process technologies should ensure this will be a constantly evolving landscape. And there will be many patient treatment options going forward.

All these developments are exciting and offer a great deal of hope. Gene and cell therapies work and save lives, and the challenge now is to scale the opportunity they offer to their full potential. Its clear that cell and gene therapy can succeed as one more healing tool. As with other treatments that moved from theoretical possibility to real results, we see the issues that need to be addressed more clearly, and were ready to get the next stage of development in motion.

References1.Cancer Statistics, National Cancer Institute: http://www.cancer.gov/about-cancer/understanding/statistics, 2018.2.Ginn S et al, Gene therapy clinical trials worldwide to 2017: An update, Journal of Gene Medicine: doi.org/10.1002/jgm.3015, 2018.

*(Article has been revised and updated)

Ger Brophy, PhD, is Executive Vice President, biopharma production at Avantor

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Opportunities and Challenges in Cell and Gene Therapy Development - Genetic Engineering & Biotechnology News

If you hit enough specific diseases, youre getting at the core aging components that are common to all of them, Church, a Wyss core faculty member, said in an interview Monday. Gene therapy gives you a testable therapy at scale in mice. And we can move from mice to dogs and then to humans. Were focusing on the reversal of age-related diseases so well be more healthy and youthful later in life.

The research is part of a broader emerging field, sometimes called geroscience. Its advocates believe that the best way to treat a variety of illnesses from cancers and heart disease to Alzheimers and macular degeneration is to attack the aging process itself.

Were taking a holistic approach, said Noah Davidsohn, a former research scientist in Churchs lab who is first author of the study. Rather than attack specific diseases, were trying to make patients generally healthier and, in the process, getting rid of as many age-related diseases as possible. Nobody wants to be old and in a wheelchair and not doing anything.

Bostons biomedical hub has become a hotbed of geroscience research.

Last winter, 16 of the worlds top longevity scientists, including Harvard scientist David Sinclair, professor of genetics and director of the Paul F. Glenn Center for the Biology of Aging, formed a Boston-based academy that will seek to spotlight medical research on extending human life and developing drugs to slow the aging process. The nonprofit Academy for Health and Lifespan Research will share research and lobby governments in the United States, Europe, and elsewhere to increase funding and create new paths to approve age-slowing therapies.

Previous studies in the field have also sought to slow aging and extend healthy life spans through small molecules that increase blood flow and endurance, or weed out zombie cells that send out toxins causing age-related maladies. But the Wyss Institute is the first to use therapy that combines genes to boost protein levels that diminish with aging. The genes were selected from a database developed over the past decade at Churchs lab.

We looked at the ones that had the biggest impact individually and then wanted to see if they would work more effectively in pairs and triples, Church said. Such an approach, he said, had the greatest potential to target multiple diseases through a one-and-done injection into the blood or muscle, a simple procedure akin to getting an influenza vaccine shot.

When deployed against obesity, type II diabetes, heart failure, and renal failure, a single formulation ... was able to treat all four diseases, according to the study published in PNAS. These results emphasize the promise of gene therapy for treating diverse age-related ailments, and demonstrate a new approach of combination gene therapy that may improve healthspan and longevity by addressing multiple diseases at once.

San Diego-based biotech startup Rejuvenate Bio, founded by Church and a pair of coauthors of the PNAS study, Davidsohn and Daniel Oliver, is pursuing a gene therapy to fight age-related diseases. The company has already begun working with the Cummings School of Veterinary Medicine at Tufts University in North Grafton to test the gene therapy combination in dogs.

Davidsohn, chief technology officer at Rejuvenate, said the company is focused for now on developing and marketing a treatment that can extend the health span of dogs, which can suffer from a range of age-related illnesses including heart and kidney problems, obesity, dementia, and hearing and vision loss similar to those afflicting humans.

His own 5-year-old dog, Bear, whom Davidsohn adopted while working in the Wyss Institute lab, was an inspiration and now holds the honorary title of chief inspiration officer at Rejuvenate. The company was launched in stealth mode about a year ago and now has eight employees.

While dogs will be an important market in their own right for the combination gene therapy, Davidsohn said, We would be happy if this ended up in humans.

Church said testing the experimental therapy in dogs is likely to take about two years. Then, if regulators approve it, clinical trials could begin in humans. But even if all goes well, he said, the gene therapy probably wont be available as a marketed product for more than a decade.

By then, he said, the cost of a gene therapy which now can top $1 million per patient for rare diseases could drop to thousands of dollars per patient in what would be a much larger market to treat multiple age-related diseases.

Some supporters of age-slowing research, such as Jay Olshansky, public health professor at the University of Illinois at Chicago, have cautioned against expectations that scientists can radically lengthen life spans. Instead, they believe, the goal should be, as Olshansky puts it, pushing out the red zone, the time of frailty and disability at the end of life.

Church, however, has a more ambitious vision.

The important thing is getting good at age reversal, he said. If age reversal truly works, there is no upper limit on how long healthy lives can be extended.

Robert Weisman can be reached at robert.weisman @globe.com. Follow him on Twitter @GlobeRobW.

Correction: An earlier version of this story incorrectly characterized the status of the collaboration between Rejuvenate Bio and George Churchs Wyss Institute Lab.

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Harvard study advances gene therapy in fighting age-related diseases - The Boston Globe

A new protein that can enhance the accuracy of CRISPR gene therapy was recently developed by researchers from City University of Hong Kong (CityU) and Karolinska Institutet. This work, published in the Proceedings of the National Academy of Sciences, could potentially have a strong impact on how gene therapies are administered in the future.

CRISPR-Cas9, often referred to as just CRISPR, is a powerful gene-editing technology that has the potential to treat a myriad of genetic diseases such as beta-thalassemia and sickle cell anemia. As opposed to traditional gene therapies, which involve the introduction of healthy copies of a gene to a patient, CRISPR repairs the genetic mutation underlying a disease to restore function.

CRISPR-Cas9 was discovered in the bacterial immune system, where it is used to defend against and deactivate invading viral DNA. Cas9 is an endonuclease, or an enzyme that can selectively cut DNA. The Cas9 enzyme is complexed with a guide RNA molecule to form what is known as CRISPR-Cas9. Cas9 is often referred to as the molecular scissors, being that they cut and remove defective portions of DNA. Being that it is not perfectly precise, the enzyme will sometimes make unintended cuts in the DNA that can cause serious consequences. For this reason, enhancing the precision of the CRISPR-Cas9 system is of paramount importance.

Two versions of Cas9 are currently being used in CRISPR therapies: SpCas9 (derived from the bacteriaStreptococcus pyogenes) and SaCas9 (derived fromStaphylococcus aureus). Researchers have engineered variants of the SpCas9 enzyme to improve its precision, but these variants are too large to fit into the adeno-associated viral (AAV) vector that is often used to administer CRISPR to living organisms. SaCas9, however, is a much smaller protein that can easily fit into AAV vectors to deliver gene therapy in vivo. Being that no SaCas9 variants with enhanced precision are currently available, these CityU researchers aimed to identify a viable variant.

This recent research led to the successful engineering of SaCas9-HF, a Cas9 variant with high accuracy in genome-wide targeting in human cells and preserved efficiency. This work was led by Dr. Zheng Zongli, Assistant Professor of Department of Biomedical Sciences at CityU and the Ming Wai Lau Centre for Reparative Medicine of Karolinska Institutet in Hong Kong, and Dr. Shi Jiahai, Assistant Professor of Department of Biomedical Sciences at CityU.

Their work was based on a rigorous evaluation of 24 targeted human genetic locations which compared the wild-type SaCas9 to the SaCas9-HF. The new Cas9 variant was found to reduce the off-target activity by about 90% for targets with very similar sequences that are prone to errors by the wild-type enzyme. For targets that pose less of a challenge to the wild-type enzyme, SaCas9-HF made almost no detectable errors.

Our development of this new SaCas9 provides an alternative to the wild-type Cas9 toolbox, where highly precise genome editing is needed, explained Zheng. It will be particularly useful for future gene therapy using AAV vectors to deliver genome editing drug in vivo and would be compatible with the latest prime editing CRISPR platform, which can search-and-replace the targeted genes.

Dr. Shi and Dr. Zheng are the corresponding authors of this publication. The first authors are PhD student Tan Yuanyan from CityUs Department of Biomedical Sciences and Senior Research Assistant Dr. Athena H. Y. Chu from Ming Wai Lau Centre for Reparative Medicine (MWLC) at Karolinska Institutet in Hong Kong. Other members of the research team were CityUs Dr. Xiong Wenjun, Assistant Professor of Department of Biomedical Sciences, research assistant Bao Siyu (now at MWLC), PhD students Hoang Anh Duc and Firaol Tamiru Kebede, and Professor Ji Mingfang from the Zhongshan Peoples Hospital.

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The larger contract manufacturing and development organization (CDMO) have developed an appetite for acquiring capabilities in the cell and gene therapy space.

For instance, Lonza filled a strategic gap in its own portfolio through the acquisition of PharmaCell providing it with a base in the Netherlands with cell and gene manufacturing capabilities.

Rival CDMOs have followed suit, with large sums changing hands in the deals that saw Thermo Fisher takeover gene therapy specialist Brammer Bio and Catalent acquire Paragon.

With increased competition in the space, some have raised concerns about the numbers of talent needed to serve this space and the challenges of keeping them once hired.

BioPharma-Reporter (BPR) spoke to Marc Funk (MF), CEO of Lonza, to gain a leadership perspective about the challenges of recruiting in the space and more broadly about the challenges facing cell and gene therapy manufacture.

BPR: Cell and gene therapy space is developing quickly how are you ensuring that talent are brought in and retained?

MF: We need to be aware of staff retention, but it's not necessarily specific to the cell and gene therapy space. The focus is training the right talent, bringing them on board, and helping the industry cope with the unmet need in cell and gene therapy. In this regard, we are not different to anybody else, but what we can say is that we do not have talent erosion people that come to our sites are happy to stay.

BPR: What are the main challenges in cell and gene therapy?

MF:The major challenge is how to make sure that the industry brings robust, scalable, industrialized manufacturing processes, as fast as possible. That's the main problem.

We are addressing this by capitalizing on our knowledge in mammalian technology, bringing in more innovation: for example, automation for autologous manufacturing and moving from 2D stacks to 3D bioreactors for allogeneic and viral vector manufacturing.

BPR: How important is automation for cell and gene therapy manufacture?

MF: For cell and gene therapies, this is an essential move that has to be accelerated. There are certain processes today that are manual but have no reason to be. That's one of the critical barriers to making the manufacturing of these medicines more robust.

BPR: Are you looking at hiring to bring in experts to improve automations? For instance, experts in AI or machine learning?

MF: We are currently doing that consciously and with high expectations that this will bring better solutions.

BPR: In particular, how do you work to entice talent to work at the Visp site?

MF: The first thing is to have a great project one that young talent can identify with. Within Lonza, that means attracting people who wish to help deliver better medicines in this world.

The second thing is to make sure that we build the right infrastructure here, in partnership with the local communities. We work closely with the authorities and schools in Valais (the Swiss canton where Visp is located) to offer apprenticeships and develop local talent. For employees coming from outside the local area, were working to make sure that the right infrastructure is in place in the region around the site, such as childcare and support for people coming to Switzerland for the first time. All of this is starting to take shape today.

BPR: How is Lonza preparing for the future?

MF: I think that the move we have made to develop the biopark here in Visp redesigning our plant and our business model is already a lesson in how we want to be set up for the future. Although we acknowledge that how we manufacture biologics will change, even within the next two to three years.

The way we are designing the plant today is set up to respond to the changes coming, with space for expansion and the flexibility that changing technology requires. But there are some things we need to do even better now, for example, improving downstream processes. That's an area that we, and the industry in general, is looking at to make sure that we have much better productivity. In addition, the industry needs to be able to bring molecules in clinical development through at a much faster pace than today.

Marc Funk has been CEO at Lonza since March 2019 and a member of the executive committee since April 2012. Prior to his time at Lonza, Funk held leadership roles at Merck Serono and Geneprot.

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Automating cell and gene therapy manufacture 'has to be accelerated', says Lonza CEO - BioPharma-Reporter.com

BRISBANE, Calif.--(BUSINESS WIRE)--Sangamo Therapeutics, Inc. (NASDAQ: SGMO), a genomic medicine company, today announced that hemophilia A gene therapy clinical data and hemoglobinopathies ex vivo gene-edited cell therapy data will be featured in poster presentations at the 61st Annual Meeting of the American Society of Hematology (ASH). The ASH abstracts, which were submitted on August 3, 2019, were released online this morning. The conference will take place in Orlando, FL, from December 7-10, 2019.

Gene Therapy

The SB-525 poster will show updated Alta study data including durability of Factor VIII (FVIII) levels, bleeding rate, factor usage, and safety, for all five patients in the high dose cohort of 3e13 vg/kg, with approximately 4 months to 11 months of follow-up after treatment with SB-525.

As of the abstract submission date, four patients in the 3e13 vg/kg cohort achieved FVIII levels within the normal range with no bleeding events reported up to 24 weeks post-administration. These patients did not require FVIII replacement therapy following the initial prophylactic period of up to approximately 3 weeks post-SB-525 administration. The fifth patient in the 3e13 vg/kg cohort had only recently undergone treatment with SB-525 at the time of the abstract submission. As previously reported, one patient had treatment-related serious adverse events (SAEs) of hypotension and fever, which occurred approximately 6 hours after completion of the vector infusion and resolved with treatment within 24 hours, with no loss of FVIII expression. SB-525 is being developed as part of a global collaboration between Sangamo and Pfizer.

The rapid kinetics of Factor VIII expression, durability of response, and the relatively low intra-cohort variability in the context of a complete cessation of bleeding events and elimination of exogenous Factor VIII usage continues to suggest SB-525 is a differentiated hemophilia A gene therapy, said Bettina Cockroft, M.D., M.B.A., Chief Medical Officer of Sangamo, commenting on the published abstract. We are pleased with the progress of the program toward a registrational Phase 3 study led by Pfizer, who announced it has enrolled its first patient in the 6-month Phase 3 lead-in study. We have recently completed the manufacturing technology transfer to Pfizer and initiated the transfer of the IND.

Ex Vivo Gene-Edited Cell Therapy

The ST-400 beta thalassemia poster will show preliminary results from the first three patients enrolled in the Phase 1/2 THALES study. In this study, hematopoietic stem progenitor cells (HSPCs) are apheresed from the patient, edited to knock out the erythroid specific enhancer of the BCL11A gene, and cryopreserved prior to infusion back into the patient following myeloablative conditioning with busulfan. The first three patients all have severe beta thalassemia genotypes: 0/0, homozygous for the severe + IVS-I-5 (G>C) mutation, and 0/+ genotype including the severe IVS-II-654 (C>T) mutation, respectively.

As of the abstract submission date, Patient 1 and Patient 2 had experienced prompt hematopoietic reconstitution. Patient 1 had increasing fetal hemoglobin (HbF) fraction that contributed to a stable total hemoglobin. After being free from packed red blood cell (PRBC) transfusions for 6 weeks, the patient subsequently required intermittent transfusions. Patient 2 had rising HbF levels observed through 90 days post-infusion. For both patients, as of the most recent follow-up reported in the abstract, on-target insertions and deletions (indels) were present in circulating white blood cells. Patient 3 had just completed ST-400 manufacturing at the time of abstract submission. As previously disclosed, Patient 1 experienced an SAE of hypersensitivity during ST-400 infusion considered by the investigator to be related to the product cryoprotectant, DSMO, and which resolved by the end of the infusion. No other SAEs related to ST-400 have been reported and all other AEs have been consistent with myeloablation. No clonal hematopoiesis has been observed. Longer follow-up will be required to assess the clinical significance of these early results. ST-400 is being developed as part of a global collaboration between Sangamo and Sanofi, along with support through a grant from the California Institute for Regenerative Medicine (CIRM).

The first three patients enrolled in the THALES study all have severe beta thalassemia genotypes that result in almost no endogenous beta globin production. The increases in fetal hemoglobin and presence of on-target indels in circulating blood cells suggests successful editing using zinc finger nucleases. The results are preliminary and will require additional patients and longer-term follow-up to assess their clinical significance, said Adrian Woolfson, BM., B.Ch., Ph.D., Head of Research and Development. It is important to note that myeloablative hematopoietic stem cell transplantation reboots the hematopoietic system, and that sufficient time is required for the stem cells to fully repopulate the marrow and for new blood cells to form. In other myeloablative conditioning studies in a similar patient population, full manifestation of the effects of gene modification in the red blood cell compartment has taken as long as 12 months or more to become evident.

Sanofis in vitro sickle cell disease poster details a similar approach to ST-400, using mobilized HSPCs from normal donors and SCD patients and utilizing the same zinc finger nuclease for gene editing, delivered as transient non-viral RNA, and designed to disrupt the erythroid specific enhancer of the BCL11A gene, which represses the expression of the gamma globin genes, thereby switching off HbF synthesis. Results from ex vivo studies demonstrated enriched biallelic editing, increased HbF, and reduced sickling in erythroid cells derived from non-treated sickle cell disease patients. Sanofi has initiated a Phase 1/2 trial evaluating BIVV003, an ex vivo gene-edited cell therapy using ZFN gene editing technology to modify autologous hematopoietic stem cells using fetal hemoglobin to produce functional red blood cells with higher BhF content that are resistant to sickling in patients with severe sickle cell disease. Recruitment is ongoing.

About the Alta study

The Phase 1/2 Alta study is an open-label, dose-ranging clinical trial designed to assess the safety and tolerability of SB-525 gene therapy in patients with severe hemophilia A. SB-525 was administered to 11 patients in 4 cohorts of 2 patients each across 4 ascending doses (9e11 vg/kg, 2e12 vg/kg, 1e13vg/kg and 3e13vg/kg) with expansion of the highest dose cohort by 3 additional patients. The U.S. Food and Drug Administration (FDA) has granted Orphan Drug, Fast Track, and regenerative medicine advanced therapy (RMAT) designations to SB-525, which also received Orphan Medicinal Product designation from the European Medicines Agency.

About the THALES study

The Phase 1/2 THALES study is a single-arm, multi-site study to assess the safety, tolerability, and efficacy of ST-400 autologous hematopoietic stem cell transplant in 6 patients with transfusion-dependent beta thalassemia (TDT). ST-400 is manufactured by ex vivo gene editing of a patient's own (autologous) hematopoietic stem cells using non-viral delivery of zinc finger nuclease technology. The THALES study inclusion criteria include all patients with TDT (0/0 or non- 0/0) who have received at least 8 packed red blood cell transfusions per year for the two years before enrollment in the study. The FDA has granted Orphan Drug status to ST-400.

About Sangamo Therapeutics

Sangamo Therapeutics, Inc. is focused on translating ground-breaking science into genomic medicines with the potential to transform patients' lives using gene therapy, ex vivo gene-edited cell therapy, in vivo genome editing, and gene regulation. For more information about Sangamo, visit http://www.sangamo.com.

Forward-Looking Statements

This press release contains forward-looking statements regarding Sangamo's current expectations. These forward-looking statements include, without limitation, statements regarding the Company's ability to develop and commercialize product candidates to address genetic diseases with the Company's proprietary technologies, as well as the timing of commencement of clinical programs and the anticipated benefits therefrom. These statements are not guarantees of future performance and are subject to certain risks, uncertainties and assumptions that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, the outcomes of clinical trials, the uncertain regulatory approval process, uncertainties related to the execution of clinical trials, Sangamo's reliance on partners and other third-parties to meet their clinical and manufacturing obligations, and the ability to maintain strategic partnerships. Further, there can be no assurance that the necessary regulatory approvals will be obtained or that Sangamo and its partners will be able to develop commercially viable product candidates. Actual results may differ from those projected in forward-looking statements due to risks and uncertainties that exist in Sangamo's operations and business environments. These risks and uncertainties are described more fully in Sangamo's Annual Report on Form 10-K for the year ended December 31, 2018 as filed with the Securities and Exchange Commission and Sangamo's most recent Quarterly Report on Form 10-Q. Forward-looking statements contained in this announcement are made as of this date, and Sangamo undertakes no duty to update such information except as required under applicable law.

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Sangamo Announces Gene Therapy and Ex Vivo Gene-Edited Cell Therapy Data Presentations at the American Society of Hematology Annual Meeting - Business...

GERMANTOWN, Md., Nov. 7, 2019 /PRNewswire/ -- Triple-Gene LLC, a clinical stage cardiovascular gene therapy company and majority owned subsidiary of Intrexon Corporation (NASDAQ: XON), today announced the completion of enrollment and dosing in its Phase 1 trial of INXN-4001, a multigenic investigational therapeutic candidate under evaluation for the treatment of heart failure, the leading cause of death worldwide. The Phase 1 open label study is designed to investigate the safety of INXN-4001 delivered via Retrograde Coronary Sinus Infusion (RCSI) in patients with an implanted Left Ventricular Assist Device (LVAD) for mechanical support of end-stage heart failure, either as a bridge to transplant or destination therapy (clinical trial identifier: NCT03409627).

"We are excited to have reached this important milestone in the clinical evaluation of INXN-4001 for treatment of end-stage heart failure," stated Amit Patel, MD, MS, Co-Founder and Medical Director of TripleGene. "Heart failure rarely results from a single genetic defect, and while single gene therapy approaches have been studied, these treatments may not fully address the causes of the disease. Our unique multigenic approach is designed to stimulate biological activity targeting multiple points in the disease progression pathway."

Triple-Gene's investigational therapy uses non-viral delivery of a constitutively expressed multigenic plasmid designed to express human S100A1, SDF-1, and VEGF165 gene products, which affect progenitor cell recruitment, angiogenesis, and calcium handling, respectively, and target the underlying molecular mechanisms of pathological myocardial remodeling. The plasmid therapy is delivered via RCSI which allows for cardiac-specific delivery to the ventricle.

"Heart failure is the leading cause of death worldwide and represents a significant and growing global health problem. Aside from heart transplant and LVAD, current treatment options for those patients with end-stage disease are limited," commented Timothy Henry, MD, FACC, MSCAI, Medical Director of the Carl and Edyth Lindner Center for Research and Education at The Christ Hospital and a member of the Triple-Gene Medical Advisory Board. "The INXN4001 investigational therapy represents a biologically-based method focused on repairing the multiple malfunctions of cardiomyocytes, and I look forward to seeing the results of this initial safety study and further exploring the promise of this innovative treatment approach."

Triple-Gene will present preliminary data from the Phase 1 study at the American Heart Association Scientific Sessionsat the Pennsylvania Convention Center in Philadelphia. A poster titled "Safety of First in Human Triple-Gene Therapy Candidate for Heart Failure Patients" will be presented on Sunday, November 17th from 3:00 pm - 3:30 pm ETin Zone 4 of the Science and Technology Hall.

About the Phase 1 Trial of INXN-4001INXN-4001 is being evaluated in a Phase I open label study in adult patients with implanted Left Ventricular Assist Device (LVAD). The study is designed to investigate the safety and feasibility of supplemental cardiac expression of S100A1, SDF-1 and VEGF-165 from a single, multigenic plasmid delivered via Retrograde Coronary Sinus Infusion (RCSI) in stable patients implanted with a LVAD for mechanical support of end-stage heart failure. Twelve stable patients with an implanted LVAD were allocated into 2 cohorts (6 subjects each) to evaluate the safety and feasibility of infusing 80mg of INXN4001 in either a 40mL (Cohort 1) or 80mL (Cohort 2) volume. The primary endpoint of safety and feasibility is assessed at the 6-month endpoint. Daily activity data are also collected throughout the study using a wearable biosensor. Dosing on both Cohorts 1 and 2 has been completed, and patients continue follow-up per protocol.

About Triple-GeneTriple-Gene LLC is a clinical stage gene therapy company focused on advancing targeted, controllable, and multigenic gene therapies for the treatment of complex cardiovascular diseases. The Company's lead product is a non-viral investigational gene therapy candidate that drives expression of three candidate effector genes involved in heart failure. Triple-Gene is a majority owned subsidiary of Intrexon Corporation(NASDAQ: XON) co-founded by Amit Patel, MD, MS, and Thomas D. Reed, PhD, Founder and Chief Science Officer of Intrexon. Learn more about Triple-Gene at http://www.3GTx.com.

About Intrexon CorporationIntrexon Corporation (NASDAQ: XON) is Powering the Bioindustrial Revolution with Better DNAto create biologically-based products that improve the quality of life and the health of the planet through two operating units Intrexon Health and Intrexon Bioengineering. Intrexon Health is focused on addressing unmet medical needs through a diverse spectrum of therapeutic modalities, including gene and cell therapies, microbial bioproduction, and regenerative medicine. Intrexon Bioengineering seeks to address global challenges across food, agriculture, environmental, energy, and industrial fields by advancing biologically engineered solutions to improve sustainability and efficiency. Our integrated technology suite provides industrial-scale design and development of complex biological systems delivering unprecedented control, quality, function, and performance of living cells. We call our synthetic biology approach Better DNA, and we invite you to discover more at http://www.dna.comor follow us on Twitter at @Intrexon, on Facebook, and LinkedIn.

TrademarksIntrexon, Powering the Bioindustrial Revolution with Better DNA,and Better DNA are trademarks of Intrexon and/or its affiliates. Other names may be trademarks of their respective owners.

Safe Harbor Statement Some of the statements made in this press release are forward-looking statements. These forward-looking statements are based upon our current expectations and projections about future events and generally relate to our plans, objectives and expectations for the development of our business. Although management believes that the plans and objectives reflected in or suggested by these forward-looking statements are reasonable, all forward-looking statements involve risks and uncertainties and actual future results may be materially different from the plans, objectives and expectations expressed in this press release.

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European regulations might be responsible for lower numbers of advanced therapy clinical trials running in the region when compared to the US and Asia.

Europe has historically been a pioneer in advanced therapies, such as cell and gene therapy. Europe was the first region to approve a gene therapy, and it boasts the highest number of marketing authorizations of advanced therapies worldwide.

However, in the past four years, the number of clinical trials with advanced therapies has stalled in Europe, growing by just below 2%. Meanwhile, the number of trials went up in North America and Asia by 36% and 28%, respectively, in the same period.

This conclusion was drawn from the analysis of the 2,097 clinical trials of advanced therapies conducted worldwide between 2014 and the first half of 2019. The study was carried out by the Alliance for Regenerative Medicine (ARM), an international community of stakeholders in the development of new medical technologies.

Current EU regulations could be to blame. Any clinical trial that is conducted across multiple European countries requires separate review and approval in each country.

When national authorities review clinical trial authorizations independently, they may have diverging opinions that create a delay for the companies, said Annie Hubert, Senior Director of European Policy at the ARM.

The issue becomes even bigger with advanced therapies, as the requirements regarding testing donors and starting materials vary across different countries.

In particular, gene therapies are the most affected. The study found that while in North America 71% of advanced therapy trials involve any form of gene therapy or gene editing, in Europe that percentage is only 55%.

Gene therapies face an additional hurdle in Europe; they are considered genetically modified organisms and must therefore additionally comply with GMO regulation, which falls under the umbrella of environmental or agricultural legislation depending on the country.

The complexity in the GMO regulation may be the reason why we see fewer clinical trials with gene therapy in Europe compared to other regions, Hubert told me.

A company that applies for a clinical trial with a gene therapy needs to secure the review and approval by the GMO authority in that country on top of having the approval for the clinical trial for the medicinal product. There have been situations where, for the same gene therapy, the decision from different GMO authorities in Europe was different.

The study concluded that streamlining the regulatory process might make Europe more competitive in the development of advanced therapies. This can already be seen in certain European countries, such as Belgium, Denmark and Switzerland, where the amount of clinical trials is actually higher than in the US when accounting for their size.

Belgium for instance has an approval time of 15 days for phase I clinical trials. That acts as an incentive, said Hubert. In the UK and in Denmark, companies have access to a central point of contact that liaises with the GMO authorities and facilitates the review of clinical trial applications.

The European Commission has been aware of these issues for several years. Previous studies reported that the current clinical trial legislation, which dates to 2001, resulted in a decline in the overall number of clinical trials running in Europe.

The Commission has already created new regulations that seek to address some of these problems through a centralized application system where one national authority takes the lead in reviewing the application, while the others can either agree or disagree with it.

However, there have been delays in the creation of the application platform and the regulations have not yet been implemented. Hubert expects this could happen sometime in late 2020 or 2021.

I think we need to be realistic. Any significant change will probably take a number of years before we can see the number of clinical trials increasing significantly in Europe.

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EU Regulations Are Holding Back Gene and Cell Therapy Clinical... - Labiotech.eu