StemCell Therapy

ARE you fed up with the usual suspects?

Fed up being unclear of what Labour stands for any more?

Fed up with the Liberal Democrats total disrespect for the popular vote?

Fed up with the old school club which the Conservatives have become?

The Liberal Party stands for an NHS focused on preventative medicine.

We stand for free vocational training and university tuition and for a de-politicised independent education commission.

We stand for reducing waste and promoting and massive investment in realistic sustainable energy solutions. We stand for reducing income tax in the lower bands, increasing inheritance tax and introducing land value tax (with reliefs for farmers).

We stand for a rural subsidy scheme based on practices which are economically sustainable, which safeguard the environment and enhance product quality.

We stand for abolishing corporation tax for start-ups. While strengthening intelligence and countering cybercrime, we oppose Trident and interventionist military actions abroad.

We believe in respecting the outcome of the referendum and seeing Brexit through. People who live in Bridgwater and West Somerset have so much to be proud of.

Lets use what weve got and promote ourselves and our products more and realise our potential as a vibrant economy that is attractive for people of all ages to live, work and visit.

Show the usual suspects that youre fed-up. Show them that its time for fresh, straight-forward, radical and truly Liberal reforms.

Vote for the Liberal Party this election!

Formerly the Theatre Manager at Strode Theatre, I am now the Exec Director of an International arts festival, and live in Chilton Polden.

I have experience in running businesses and charities, teaching and working with communities and stake-holders, having previously been an elected Councillor and worked in community-facing organisations.

Get in touch: email somersetliberals@gmail.com or call 0330 223 5773

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ELECTION PROFILE: Fares Moussa, The Liberal Party - This is The West Country

Medicine is medicine the world over, but if you studied, interned, and completed your residency in a big coastal city, then you might wonder what its like for your colleagues in the Midwest. Is life slower-paced? Is the money good? Is making the move worthwhile?

The Midwest (and rural areas across the nation, for that matter) is desperately in need of more doctors. The National Rural Health Association says that although a quarter of the U.S. lives in rural areas, only 10 percent of doctors practice in the same setting. And as the general shortage of doctors continues to grow, places like the Midwest will feel it more keenly.

Whats it like to practice medicine in the Midwest? As it turns out, it presents some of the same healthcare challenges and opportunities that you already experience elsewhere in the country.

When you practice in a coastal metropolitan area, youre likely never more than a short journey from one of the best specialists in the country. Sometimes theyre even in the same building. As a result, you can rely on an extensive network of colleagues and professionals to consult with and to direct patients to often with a click of a button. When you live and practice in most parts of the Midwest (bar Chicagoland), however, you dont always have that option.

Physicians in the Midwest say that they find the scope of their practice is much wider than it needs to be elsewhere, and the depth of knowledge required is deeper than it needs to be elsewhere. You can consult research articles and email doctors further afield from your local office, but you wont meet the worlds top specialists in your hospitals physician lounge. Youre well off if you have a decent ER in the area, enough family physicians to take time off, and a general surgeon. And because a substantial number of your patients wont or cant afford to travel, you need to be able to treat more conditions yourself while still using the best available, evidence-based medicine.

Interviews from a new documentary, The New Country Doctor, also suggest that its not enough to be the best-of-the-best in terms of your medical skills. You also need to be excellent at making connections. Not only do your professional connections take more work, but youll need to develop new resources in unexpected places. You may also need to have the skills to seek out and engage with community resources as you connect patients with county or state mental health resources, housing resources, and even food programs. Given the ongoing opioid epidemic, you will also need to get creative when hunting down resources for chronic pain sufferers.

States like Indiana are famous for low cost of living: even Indianapolis is incredibly affordable, particularly for a capital city. As a doctor in a Midwestern state, youll find that its much easier to afford rent or a mortgage, and even pay off your student debt much faster as a result. You may even qualify for student loan forgiveness programs designed to encourage doctors to practice in underserved areas.

At the same time, you may still work longer hours than you might in a highly-structured environment elsewhere. Outside of the metropolitan areas of Chicago, St. Louis, and Minneapolis-St Paul, patient populations not only have fewer health care options, but the agricultural community often presents offbeat schedules. You may find yourself offering evening appointments and making housecalls. Additionally, you may work in a health care system with less support staff than youre used to, leaving more of the administrative up to you and increasing your work week that way.

Your hours may even extend more stealthily than simply staying open later. Small towns, in particular, physicians are friends, coworkers, and family members. The interpersonal dynamics of living in small to medium Midwestern towns can mean that youre on duty both at the clinic and when out to eat with your spouse. As noted by Kathleen Miller in the AMA Journal of Ethics, the overlapping roles in your community mean you are very visible, privacy is hard to find, and it can be hard to separate your personal and professional life, which can take its toll on your marriage and family relationships.

It can be strange to fathom, but when you work in small towns, you arent just missing the latest technology. You may not even have full-time access to an MRI machine, much less the access to medical artificial intelligence technology. Without the basics covered, you need to learn to prioritize your technology and insist on the basics.

Out here, technology in medicine isnt just about increasing the hospitals ROI or competing with another health organization. Technology can transform patient care for both rural and urban patients in the Midwest by helping them avoid long, expensive trips to high-end facilities.

Telemedicine is one thing that most rural and even suburban doctors in the region can and often have to advocate for. Depending on where you settle, it may not even be available yet. But telehealth can improve both preventative care and emergency care, as well as mental health care through the help of social workers. For example, if you suspect a patient is presenting symptoms of a stroke, you can teleconference with a neurologist and get them their anti-clotting medication ASAP and therefore improving patient outcomes.

Practicing medicine in the Midwest comes with new challenges that push you both as a medical professional and as a person.

You probably wont get to enjoy the same resources that come with practicing in a large, well-funded hospital, but you will have a chance to make a real difference in peoples lives and become an essential part of a community. You can even be part of a systemic change that relieves the health inequities that rural Americans face every day.

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What's It Like to Be a Doctor in the Midwest? - Muncie Voice

Jaguar and Land Rover cars are joining the fight against superbugs and killing them in their cars air conditioning units before they can infect their occupants.

The automaker is fitting future models of its vehicles with an ultraviolet light (UVC) to sterilise the interior of the cars.

UV lights have been used in the medical world for more than 70 years and is effective at killing pathogens including bacteria and viruses.

High energy rays from UV light sterilise the contents of the air conditioning system before it is pumped around the cars cabin, reducing the risk of infection.

Scroll down for video

UV technology is already used for disinfecting water, filtering air and sterilising surfaces but the move to implement it in a car would be a first for the industry.

Exposing pathogens to UVC destroys bonds within the DNA of the harmful microorganism and renders it useless and harmless to humans.

Healthcare and maintaining the well-being of the driver and other occupants is a growing priority for Land Rover and Jaguar, who are owned by the same firm.

Its current heating, ventilation and air conditioning (HVAC) systems, which are available inthe all-electric Jaguar I-PACE and Range Rover Sport, uses high voltage to manipulate air particles.

The firm claims trillions of nano-sized negatively charged particles (ions) deactivate pathogens by forming larger particles.

These are then trapped by the cars filters and discarded.

Ion technology such as this, Jaguar Land Rover claims, is also effective at getting rid of smells and allergens.

Dr Steve Iley, Jaguar Land Rover Chief Medical Officer, said: The average motorist spends as much as 300 hours per year behind the wheel. There is a clear opportunity to better utilise cars for administering preventative healthcare.

The firm claims UVC technology in cars would be able to stop the spread of cold and flu while also reducing the transmission of major superbugs by up to 30 per cent.

Immunology expert, Dr Hellmut Mnch, CEO at Medical Enzyme Research Association, added: The rise of superbugs and allergens is one of the largest threats we face as a species today.

Investment in immunology is vital in ensuring that our immune systems stay ahead of the race against microorganisms, which are evolving far quicker than traditional pharmaceuticals can keep pace with.

It is important that we continue to take an innovative look at how we can adapt our environment to help prevent the spread of the most harmful pathogens which is why this research is paramount.

Antibiotics have been doled out unnecessarily by GPs and hospital staff for decades, fueling once harmless bacteria to become superbugs.

The World Health Organization has previously warned if nothing is done the world was headed for a post-antibiotic era.

It claimed common infections, such as chlamydia, will become killers without immediate answers to the growing crisis.

Bacteria can become drug resistant when people take incorrect doses of antibiotics, or they are given out unnecessarily.

Chief medical officer Dame Sally Davies claimed in 2016 that the threat of antibiotic resistance is as severe as terrorism.

Figures estimate that superbugs will kill ten million people each year by 2050, with patients succumbing to once harmless bugs.

Around 700,000 people already die yearly due to drug-resistant infections including tuberculosis (TB), HIV and malaria across the world.

Concerns have repeatedly been raised that medicine will be taken back to the dark ages if antibiotics are rendered ineffective in the coming years.

In addition to existing drugs becoming less effective, there have only been one or two new antibiotics developed in the last 30 years.

In September, the World Health Organisation warned antibiotics are running out as a report found a serious lack of new drugs in the development pipeline.

Without antibiotics, caesarean sections, cancer treatments and hip replacements would also become incredibly risky, it was said at the time.

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Jaguar is building a car that could stop you catching a cold - Stock Daily Dish

Family Photo

Warren Bobrow=WB: Please tell me about yourselves? Where are you from? What was your path to your healing with cannabis? Who were your mentor(s)?

Phiton Nguyen=PN: Growing up in Orange Countys Little Saigon as second-generation immigrants from Vietnam, my sister and I had an ideal environment to explore our mutual interests in nature and health. I was interested in cannabis plants from an early age and even grew 8 plants in our backyard when I was 13. Most recently, I spent several years in the e-cigarette industry pursuing another interest born out of curiosity more than personal use, and learned the mechanics of vaporizer technology. At the time, devices on the market were complicated to use and sometimes downright unsafe, usually designed for self-learned or inexperienced users. I was intrigued by the challenge of engineering a vaporizer that was well designed, safe, high quality, and practical for ex-smokers who wanted to offset health risks. Our parents have been our greatest supporters and mentors. They overcame unimaginal hardship as refugees during the Vietnam War and were able to start a renowned record company, Lang Van once they came to America. Their entrepreneurial spirit and business acumen has guided many of our critical decisions as a young company.

QWIN logo w bar (1)

Mimi Nguyen=MN: We began to explore the medicinal uses of cannabis after my mom and I were both diagnosed with cancer. Thankfully, we are both in remission now, but the experience was serious wake up call for our entire familys health. We collectively developed more health-conscious habits and started researching the benefits of cannabis and Eastern medicine. When California legalized recreational cannabis, we began exploring the potential applications of cannabis as a wellness tool. While there were countless options available on the market, we realized that the majority of those products were designed in a way that mitigated the plants nutrient-rich and medical benefits when consumed. When eaten, at least half of the cannabinoids are effectively lost to the digestive process, and while inhalation allows a higher absorption rate of cannabinoids, many arrive dormant or destroyed by the heat used in standard methods of combustion. Phitons expertise in vaporizer technology and our familys penchant for holistic experimentation converged as a family pursuit of smarter cannabis consumption, leading us to create the product that becameQWIN.

WB: Why CBD? Where do you source your products from?Tell me about your company a bit more? What is micro-fusion technology? How do you determine dosages?

PN & MN: We believe that CBD has the potential to help individuals who depend on medications that are either addictive or have adverse side effects to manage chronic physical or mental conditions. We wanted to create a natural source of relief for anyone who is spending numerous hours a day dealing with pain, anxiety, or distress. Our CBD is sourced from an extraction facility in Milwaukee that is also USFDA approved for bottling and is in the process of being CGMP certified.QWINs MicroFusion technology is an ultrasonic emulsion process where we create a more bioavailable formula where the CBD becomes more absorbent particles that your body can process faster and more efficiently. The process also infuses food-grade flavors into each formula and creates an effective product and maintain a lower cost to the user. We designed QWIN to be used frequently throughout the day to give our customers a steady and balanced feeling. Each CBDi cartridge contains 100 mg of full-spectrum CBD and approximately 45 doses. We do not have a recommended dosage amount because each body is different, but users should feel the effects within 5 minutes of inhaling and can decide if they need more from there.

WB: Did you go to B-School (or school of hard knocks)? What is your professional background in this field? What is your six month and twelve month plan?

MN: I went to Chapman University for film production and did not have a formal business education, but being involved in my familys music business at a young age gave me the skills and insight to runQWIN. I manage the legal aspects of every project, design our digital licensing program for our entire catalogue of music and videos, and lead the acquisition of our cannabis facility and licenses. In the next six months, we expect to have a fully licensed cannabis manufacturing and distribution facility, launch a line of high potency CBD and microdose THC capsules, and focus on building our educational and influencer partnership divisions.

PN: I went to UC Santa Cruz for printmaking and mathematics and also learned how to manage a production facility producing artists which taught me the day-to-day business operations and distribution of entertainment from our parents business. My product development background helped me design and launch QWINs innovative technology. During my five years in the industry, Ive developed several product lines in hardware technology and e-liquid brands. In 12 months, we hope that other vape companies will use QWINs technology and platform in their own products.

WB What kind of stigmas do you face? How do you anticipate removing these obstacles? What do you see as the future of wellness?

PN & MN: The entire vape industry has received a lot of negative press due to the rise in lung illnesses linked to illicit THC cartridges. The media has characterized all vape use as dangerous, which is vastly misguided. Inhaling medicine has been around for decades and is one of the most effective methods for instant relief. The only way to challenge this misperception is through public education. Just like how cannabis use was widely vilified decades ago, people are often scared of what they do not know. We see this current vape crisis as an opportunity to engage with consumers and health officials about the benefits of vaping legal CBD and THC and will diligently work with testing labs to reinforce that our products are safe. The future of wellness lies in taking a preventative approach by having access and education to natural remedies and learning how to be more mindful of our health choices.

Kits-CBDi-Starter (1)

WB: What is your passion?

PN: I love developing products that can enhance peoples life experiences. Some of the most life-changing products ever created resulted in incremental changes that made a significant difference in peoples lives. While we cant solve the underlying problems that cause chronic health issues, what we can do is give individuals a natural tool to make their lives easier as they navigate this challenge.

MN:The Mongo verb temu comes to mind. It roughly translates to, I believe that I am not passionate about one particular thing, but a way of living life. I want to be in a constant state of inspiration, always creating and rushing to create holistic solutions for individuals trying to improve their quality of life.

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Meet The Family Behind QWIN: Revolutionizing CBD Technology - Forbes

BOSTON (PRWEB) November 28, 2019

Aesthetic tourism is especially developed in Thailand, where 20% of all patients are from abroad. Hair transplant is one out 5 of the most popular surgeries and the most frequently performed cosmetic procedures for men.

Hair transplant: facts and figures

Revolutionary methods of hair plantation

High demand gives rise to great discoveries. Doctors around the world are working on the development of new therapies that will help solve the hair loss issue by minimizing risks and reducing treatment time.

Except for the traditional hair transplant methods as FUE (follicular unit extraction) and FUT (follicular unit transplant), specialists apply stem cell hair restoration and robotic operation.

A doctor chooses the most effective treatment method according to your personal features and test results.

Hair transplant market trends

The hair transplant market is one of the fastest-growing health care specialties. The market size of hair plantation has developed by 64% since 2014, according to ISHRS statistics, and accounts for 6.5 billion USD.

Four factors are affecting the surgical hair restoration market:

1. the increasing number of people who suffer from baldness over the world2. the growing interest in self-care procedures within the Asia Pacific region3. development of minimally invasive and painless hair transplant techniques4. changing lifestyles globally.

Because of the high demand, there are a lot of clinics providing this procedure at different prices. According to Bookimed stats, the lowest hair transplant cost is offered in India and Turkey due to the general price policy within the country and residents' living wage. Patients also choose the UAE, Thailand, and South Korea in the interest of the combination of affordable prices and vacation.

About this study

This research is conducted by the Bookimed team and based on:

About Bookimed

Bookimed is a global platform for matching medical facilities over the globe and arranging the medical trip in the shortest term. Over 300,000 users from almost 30 countries request Bookimed to get treatment assistance each month.

Bookimed is a medical tourism provider that cooperates with 340 medical centers to help each patient receive timely and high-quality health care. The services of this platform are free of charge for patients because all the proceeds Bookimed gets from the partner clinics.

For more information, visit The Treatment blog or follow Bookimed on Facebook and Twitter.

Related Linkshttps://bookimed.com/

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Every 13th man has a hair transplant according to Bookimed study - PR Web

(Reuters) - Eleven drugmakers led by Pfizer and Novartis have set aside a combined $2 billion to invest in gene therapy manufacturing since 2018, according to a Reuters analysis, in a drive to better control production of the worlds priciest medicines.

FILE PHOTO: A logo for Pfizer is displayed on a monitor on the floor at the New York Stock Exchange (NYSE) in New York, U.S., July 29, 2019. REUTERS/Brendan McDermid

The full scope of Novartis (NOVN.S) $500 million plan, revealed to Reuters in an interview with the companys gene therapy chief, has not been previously disclosed. It is second only to Pfizer (PFE.N), which has allocated $600 million to build its own gene therapy manufacturing plants, according to filings and interviews with industry executives.

Gene therapies aim to correct certain diseases by replacing the missing or mutated version of a gene found in a patients cells with healthy copies. With the potential to cure devastating illnesses in a single dose, drugmakers say they justify prices well above $1 million per patient.

But the treatments are also extremely complex to make, involving the cultivation of living material, and still pose a risk of serious side effects.

Drugmakers say building their own manufacturing plants is a response to rising costs and delays associated with relying on third-party contract manufacturers, which are also expanding to capitalize on demand.

They say owning their own facilities helps safeguard proprietary production methods and more effectively address any concerns raised by the U.S. Food and Drug Administration (FDA), which is keeping a close eye on manufacturing standards.

Theres so little capacity and capability at contract manufacturers for the novel gene therapy processes being developed by companies, said David Lennon, president of AveXis, Novartiss gene therapy division. We need internal manufacturing capabilities in the long term.

The approach is not without risks.

Bob Smith, senior vice president of Pfizers global gene therapy business, acknowledged drugmakers take a leap of faith when they make big capital investment outlays for treatments before they have been approved or, in some cases, even produced data demonstrating a benefit.

The rewards are potentially great, however.

Gene therapy is one of the hottest areas of drug research and, given the life-changing possibilities, the FDA is helping to speed treatments to market.

It has approved two so far, including Novartiss Zolgensma treatment for a rare muscular disorder priced at $2 million, and expects 40 new gene therapies to reach the U.S. market by 2022.

There are currently several hundred under development by around 30 drugmakers for conditions from hemophilia to Duchenne muscular dystrophy and sickle cell anemia. The proliferation of these treatments is pushing the limits of the industrys existing manufacturing capacity. Developers of gene therapies that need to outsource manufacturing face wait times of about 18 months to get a production slot, company executives told Reuters.

They are also charged fees to reserve space that run into millions of dollars, more than double the cost of a few years ago, according to gene therapy developer RegenxBio.

As a result, companies including bluebird bio (BLUE.O), PTC Therapeutics (PTCT.O) and Krystal Biotech (KRYS.O) are also investing in gene therapy manufacturing, according to a Reuters analysis of public filings and executive interviews.

They follow Biomarin Pharmaceutical Inc (BMRN.O), developer of a gene therapy for hemophilia, which constructed one of the industrys largest manufacturing facilities in 2017.

The FDA is keeping a close eye on standards.

This comes amid the agencys disclosure in August that it is investigating alleged data manipulation by former executives at Novartis AveXis unit.

AveXis had switched its method for measuring Zolgensmas potency in animal studies. When results using the new method didnt meet expectations, the executives allegedly altered the data to cover it up, the FDA and Novartis have said.

One of the former executives, Brian Kaspar, denied wrongdoing in a statement to Reuters. Another, his brother Allan Kaspar, could not be reached for comment.

Novartis and the FDA say human clinical trials, which found Zolgensma effective in treating the most severe form of spinal muscular atrophy in infants, were not affected. Novartis also says its investments in gene therapy production started long before it became aware of the data manipulation allegations.

But the scandal has highlighted the importance of having a consistent manufacturing process for gene therapies, industry executives say.

According to four of them, the FDA has stressed in recent meetings the need for continuity in production processes all the way from the development of a drug to its commercialization.

By bringing production in-house, drugmakers may avoid pitfalls such as the need to switch to a larger facility if contract manufacturers capacity proves limited, executives say.

The FDA is finalizing new guidelines for gene therapy manufacturing, expected at the end of the year.

Manufacturing consistency is always a major concern for the agency, FDA spokeswoman Stephanie Caccomo told Reuters.

Highlighting the pressures on the industry, Sarepta Therapeutics (SRPT.O), which largely outsources manufacturing, delayed a clinical trial of its Duchenne treatment in August, telling investors it wanted to avoid any questions from regulators about consistency in producing its therapy at commercial scale.

Between the trade secrets, the cost schedules and the time lag, it makes a whole lot of sense, if you can do it, to build out your own facilities and more and more gene therapy companies have started to do that, said Krish Krishnan, chief executive of Krystal Biotech Inc.

Krystal, which is developing therapies for rare skin diseases, has built one manufacturing facility and plans to invest more than $50 million in a new one it will start constructing in December.

MeiraGTx (MGTX.O), which focuses on gene therapies for eye conditions, estimates it is currently spending roughly $25 million a year on manufacturing, including process development.

Despite such moves, however, contract manufacturers like Lonza (LONN.S) and Thermo Fisher (TMO.N) are confident their businesses will continue to grow due to the strength of demand.

Thermo Fisher has told investors its Brammer gene therapy manufacturing division, acquired in May, could soon earn $500 million in revenue a year, double its projected 2019 earnings. Lonza CEO Marc Funk is also optimistic.

Demand in gene therapy has increased, he said in an interview. We believe this is going to continue in the coming years.

Reporting by Carl O'Donnell in New York and Tamara Mathias in Bengaluru; Editing by Tomasz Janowski, Michele Gershberg and Mark Potter

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Pfizer, Novartis lead $2 billion spending spree on gene therapy production - Reuters

27 Nov 2019

Twenty years ago, researchers took fibroblasts from the skin of eight Alzheimers patients, engineered them to produce nerve-growth factor, and slid them into each volunteers basal forebrain. They hoped the neurotrophin would halt or slow the neurodegeneration that robbed them of their memories, indeed their lives. The gamble failed and since then, scientists have shown little zest for gene therapy in neurodegenerative disorders. That is changing. As evident at this years Society for Neuroscience conference, held October 1923 in Chicago, gene therapy is back. Buoyed by success in treating spinal muscular atrophy in infants, scientists are flush with new ideasand funding.

What was once considered risky, expensive, and unlikely to succeed is now seen by many as risky, expensiveand quite likely to succeed. A growing number of scientists think gene-based therapies may have the best chance of slowing, or even preventing, neurodegeneration, especially for disorders caused by mutations in a single gene. SfN hosted a press briefing on gene therapy, plus many projects are active throughout the field beyond those showcased at the conference. There was no breaking clinical trial news at the annual meeting, but the scope and challenges of such therapies were outlined at the briefing moderated by Rush University s Jeff Kordower, Chicago, as well as a translational roundtable moderated by Asa Abeliovich, Columbia University, New York. Abeliovich recently co-founded Prevail Therapeutics, New York.

Going viral. Researchers are tweaking the capsid of adeno-associated viruses to optimize gene therapies for a multitude of disease. Shown here, AAV2.

From Zolgensma to Alzheimers? If the failure of the nerve growth factor therapy tempered enthusiasm for gene therapy (Mar 2018 news), then the success of AVXS-101, aka Zolgensma, reignited it. Developed by scientists at Nationwide Childrens Hospital, Columbus, Ohio, and AveXis, Bannockburn, Illinois, AVXS-101 uses an adeno-associated virus to deliver billions of copies of the survival motor neuron 1 gene to the brain. A small pilot trial tested the therapy in babies with spinal muscular atrophy (SMA) Type 1, the severest form of this neurodevelopmental disease. Lacking functional SMN1, these infants face progressive muscle weakness. Most die before their second birthday; those who live need a ventilator to breathe.

In Phase 1, AVXS-101 dramatically improved motor function of 15 treated infants; all were living 20 months later when historical data predicted only one would survive. Twelve babies who received the highest dose grew stronger within months, most sitting independently and rolling over. They hit the highest score on a scale of motor function, whereas untreated babies deteriorated. By 20 months, two of the treated babies had begun to walk (Mendell et al., 2017). The Food and Drug Administration approved zolgensma in May 2019. At SfN in Chicago, Petra Kaufmann, AveXis, played videos of the first patients treated with AVXS-101. Some four years later, they are walking, running, and appear to be playing almost normally. A video of a little girl walking downstairs with nary a hint of having SMA Type I visibly moved the audience.

Scientists say its a game-changer. It is really the tremendous success with SMA that has renewed interest in gene therapy, said Clive Svendsen, Cedars-Sinai Regenerative Medicine Institute, Los Angeles. Speaking with Alzforum before SfN, Bart De Strooper, Dementia Research Institute, London, said the same. The success in SMA patients of both gene therapy and antisense therapy has revived interest in the whole area, De Strooper said. Nowadays, researchers tend to lump gene therapy and antisense therapy under one moniker, i.e., gene-based therapy. The SMA antisense therapy nusinersen also works in babies with SMA Type 1 and is FDA-approved (Nov 2016 news; May 2018 conference news). Unlike gene therapy, antisense therapy needs to be delivered indefinitely.

How About Neurodegenerative Disease?At SfN, scientists outlined strategies for treating adults who face years of decline due to Alzheimers, amyotrophic lateral sclerosis, frontotemporal dementia, Huntingtons (HD) and Parkinsons diseases (PD), or other synucleinopathies. Some are being tested in clinical trials, others are in preclinical development. Some target specific losses or gains of function, others aim to rescue dying neurons more broadly. Scientists also believe that working on rare childhood diseases of lysosomal storage may give them an opening to treat this common phenotype in age-related neurodegeneration, as well.

Just this October, an ApoE gene therapy trial started enrolling. Led by Ronald Crystal at Weill Cornell Medical College, New York, it will inject adeno-associated virus carrying the gene for ApoE2 into patients with early to late-stage AD who inherited two copies of ApoE4. The idea is to flood their brains with the protective allele of this apolipoprotein to try to counteract the effects of the risk allele. AAV-rh10-APOE2 will be injected directly into the subarachnoid cisternae of participants brains. The Phase 1 trialwill recruit 15 patients with biomarker-confirmed AD. Beverly Davidson, Childrens Hospital of Philadelphia, has a similar ApoE2 gene therapy in preclinical development.

At SfN, Abeliovich detailed Prevails programs for forms of PD and for frontotemporal dementias that are caused by risk alleles. A trial has begun for a glucocerebrosidase-based gene therapy. The enzyme GCase is essential for lysosomes to function properly. People who have loss-of-function mutations in both copies of the GBA1 gene develop Gauchers, a lysosomal storage disease. The severest form starts in babies, most of whom die before age 2. Milder forms cause later-onset Gauchers, while heterozygous mutations in GBA1 increase risk for Parkinsons, making restoration of GCase an obvious strategy for PD. Some researchers are trying to develop ways to boost activity of the mutated enzyme (e.g., Oct 2019 news), whereas Abeliovich and colleagues have constructed AAV-9 vectors to deliver normal GBA1 into the brain to restore GCase production.

In preclinical studies, the AAV9-GBA1 construct PR001 rescued both lysosomal and brain function in models of GCase deficiency and of Parkinsons, Abeliovich said. In mice fed the GCase inhibitor conduritol epoxide (CBE), PR001 injected into the brain ventricles beefed up GCase activity and reduced glycolipid accumulation, which is a sign that lysosomes are functional. A single dose worked for at least six months. Similar results were seen in a commonly used model of Gauchers that expresses the V394L GBA mutation and only weakly expresses prosaposin and saposins, lysosomal proteins that metabolize lipids. In these 4L/PS-NA mice, PR001 made increased levels of active GCase, fewer lipids accumulated, and the mice were more mobile on a balance beam. 4L/PS-NA mice also accumulate -synuclein, the major component of Lewy bodies in PD and other synucleinopathies. In these mice, and also in A53T -synuclein mice made worse with CBE, PR001 halved the amount of insoluble -synuclein, Abeliovich reported at SfN.

In search of the right dose for humans, the scientists next turned to nonhuman primates. They injected PR001 into the cisterna magna in hopes AAV9 would broadly distribute throughout the brain. At the highest dose, 8 x 1010 capsids per gram of brain weight, exposure in the brain was similar to that seen in the mice. The virus permeated the spinal cord, frontal cortex, hippocampus, midbrain, and putamen.

Also in October, Prevail scientists began recruiting for a Phase 1/2 double-blind, sham-controlled trial to test this gene therapy in 16 people with moderate to severe PD, who have mutations in one or both copies of their GBA1 genes. Six patients each will receive a low or high dose of PR001A. Blood and CSF biomarkers to be analyzed at three and 12 months, and at follow-up, include GCase, lipids, -synuclein, and neurofilament light chain. Participants will also undergo cognitive, executive, and motor-function tests and brain imaging. A Phase 1/2 trial of PR001 in neuronopathic Gauchers, which affects the brain and spinal cord, will start soon, Abeliovich said.

Other groups are boosting dopamine production in Parkinsons by way of gene therapy. VY-AADC,developed by Voyager Therapeutics, Cambridge, Massachusetts, packages the gene for L-amino acid decarboxylase (AADC), which converts L-dopa into dopamine, in an AAV-2 vector that is delivered into the brain. Two Phase 1 open-label trials are testing safety and efficacy. Both the PD-1101 and PD-1102 trials use MRI to guide injections of the vector bilaterally into the putamina of 15 or 16 patients, respectively. According to preliminary results presented at the annual meeting of the American Academy of Neurology this past May, the virus penetrated half of the putamen and AADC activity, as judged by 18F-DOPA PET, increased by 85 percent in the latter study. Seven of eight treated patients reported improvement after a year, along with longer on time on L-DOPA, and shorter off time. Off time is the period when L-DOPA effects wear off and patients experience loss of motor control. RESTORE-1, a Phase 2 study of 42 patients, started in 2018 and will run to the end of 2020.

Long-Lived Gene Therapy. When a Parkinsons disease patient died eight years after neurturin gene therapy, the trophin was still being expressed in their putamen (top left) and substantia nigra (bottom left), where it corresponded with tyrosine hydroxylase activity (right). [Courtesy of Jeff Kordower.]

Also in PD, Kordower and colleagues plan to re-evaluate neurturin-based gene therapy. Previously, the gene for this neurotrophin was delivered in an AAV2 vector into the brains of Parkinson patients in Phase 1 and 2 trials. This did not improve motor function. Even so, in Chicago Kordower showed that in two patients who died eight and 10 years later, the inserted gene was still expressing neurturin and that dopamine levels were higher on the injected than the contralateral side of the substantia nigra/putamen. This shows us that long-term gene expression can be achieved in the human brain, said Kordower (see image above). He believes that by focusing delivery with ultrasound, or tweaking the capsid itself, he may be able to generate enough gene expression to improve function.

Separately, AAV-GAD, a gene therapy for PD that showed promise in Phase 2 (Mar 2011 news) was acquired by MeiraGTx, New York, which will continue to develop it in the U.S. and Europe, according to founder Samuel Waksal (Nov 2018 news).

For its part, Prevail has a gene transfer construct for frontotemporal dementia in the pipeline, as well. Called PR006, it carries GRN, the gene encoding progranulin, on an AAV9 vector. GRN mutations cause familial FTD and, much like GBA mutations, do their dirty work via lysosomal dysfunction. In Chicago, Abeliovich reported that PR006 boosted progranulin release from neurons derived from FTD-GRN patients, nearly doubling their levels of mature Cathepsin D, the lysosomal protease that chops progranulin into granulins and indicates healthy lysosomes. In progranulin knockout mice, PR006 restored brain GRN expression and progranulin secretion into the CSF. Abeliovich said he expects a Phase 1/2 clinical trial in FTD patients to start in early 2020.

The biotech company Passage Bio, Philadelphia, is planning for clinical trials early next year with its AAV-GRN vector. MeiraGTx, New York, is banking on a different approach for FTD. They have developed an AAV carrying UPF1, which encodes regulator of nonsense transcripts 1. This protein helps clear out aberrant RNAs through a process call nonsense-mediated decay. MeiraGTx hopes this will restore homeostasis to RNA processing. AAV-UPF1 will be trialed for FTD and all forms of ALS bar those caused by mutations in SOD1. For SOD ALS, Novartis, Basel, Switzerland, and REGENXBIO, Rockville, Maryland, have a vector in preclinical testing.

For his part, Svendsen is taking a different approach. His lab tackles ALS with ex vivo gene therapy. The idea is to engineer clinical-grade human stem cells to produce glial-derived growth factor, and inject them into the spinal cord, much like the early NGF studies did in AD. Svendsen hopes the cells will churn out enough of the neurotrophin to protect spinal cord motor neurons. In a Phase 1/2a trial, 18 ALS patients have received these cells into one side of their spinal cords, such that each person serves as his or her own control. If this works, they would regain mobility only on the injected side. The trial finished in October; Svendsen expects results to come out in a few months. In a follow-up study, the scientists are trying to do the same with induced pluripotent stem cells. This would allow them to transplant autologous cells into patients, avoiding immune rejection

Other groups are deploying gene therapy as a way to improve immunotherapy, shield neurons from stress, or even generate neurons from astrocytes to make up for those lost to neurodegeneration.Tom Fagan

Read the rest here:
Time to Try Again: Gene-Based Therapy for Neurodegeneration - Alzforum

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Link:
Novartis opens new cell and gene therapies facility in Switzerland - Pharmaceutical Business Review

Traditional gene therapy has seen numerous challenges during its decades of development, but scientists seem to have finally figured out how to get the treatment to work with regulatory approvals forNovartis' (NYSE:NVS) Zolgensma and bluebird bio's (NASDAQ:BLUE) Zynteglo this year. The process involves inserting genes into diseased cells to express missing or mutated proteins.

Storming onto the scene over the past few years, CRISPR/Cas9, championed by CRISPR Therapeutics (NASDAQ:CRSP), Editas Medicine (NASDAQ:EDIT) and Intellia Therapeutics (NASDAQ:NTLA), offered hope for more precise gene editing. At the very least, the process can insert the gene into a precise location in the genome. More impressive -- and something that traditional gene therapy can't readily do -- CRISPR/Cas9 offers the possibility of deleting problematic genes or making specific changes to mutated genes to restore their functions.

Image source: Getty Images.

CRISPR/Cas9 appeared to be working well in preclinical models, and last week, investors got a first look at how the therapy is working in humans with CRISPR Therapeutics and its development Vertex Pharmaceuticals (NASDAQ:VRTX) announcing results for the first two patients treated with CTX001.

One patient with a blood disorder called transfusion-dependent beta thalassemia (TDT) required 16.5 transfusions per year over the two years before being treated with CTX001, but nine months after treatment, the patient was transfusion independent with high expression of fetal hemoglobin, the gene inserted into the patients' cells.

The other patient had sickle cell disease (SCD) with an average of seven vaso-occlusive crises (VOCs) per year over the two years before the study started. Four months after being treated with CTX001, the patient was free of VOCs, which are caused by sickle-shaped red blood cells that block blood vessels. Like the beta thalassemia patient, the SCD patient had expression of fetal hemoglobin.

The results from the first two patients look comparable to Bluebird's Zynteglo, which also treats TDT and SCD by increasing hemoglobin levels. But this was data from just two patients, and investors should still have plenty of questions as we get additional data:

Consistency: One patient in each disease doesn't say much about how well the treatment works in the average patient. What will the efficacy look like after the treatment of a few dozen patients?

Durability: Gene editing and gene therapy are designed to be cures. Do both last forever?

Manufacturing: Bluebird had to adjust its manufacturing procedure to increase expression to treat patients requiring higher expression. Will the initial CRISPR/Cas9 manufacturing procedure work for all patients?

In vivo/ex vivo: That's Latin for in or outside of a living thing -- in this case a human being. CTX001 and Zynteglo are ex vivo treatments because cells are taken from the patient, manipulated to express the gene of interest, and put back into the patient. Novartis has shown that gene therapy can work in vivo with Zolgensma delivered via an injection of a viral vector. Can CRISPR/Cas9 work in vivo in humans? Editas Medicine hopes so, but the company still hasn't advanced a treatment into the clinic.

Last week's data release offers plenty of hope for investors in CRISPR/Cas9 and traditional gene therapy companies should certainly be looking in the rearview mirror at the technology coming up from behind, but it's still way too early to pick a winner between traditional gene therapy and CRISPR/Cas9.

The right answer for investors in biotech companies might end up being to buy both. The upside potential for curing diseases may end up outweighing the downside if one technology doesn't end up working out.

See original here:
CRISPR vs. Gene Therapy Round 1: What Investors Need to Know - The Motley Fool

Pfizer and Novartis lead eleven drug manufacturers setting aside a combined $2bn to invest in gene therapy manufacturing since 2018.

According to a Reuters analysis, this strategy aims to better control production of the worlds priciest medicines.

The full scope of Novartis $500mn plan, revealed to Reuters in an interview with the companys gene therapy chief, has not been previously disclosed. It is second only to Pfizer, which has allocated $600mn to build its own gene therapy manufacturing plants, according to filings and interviews with industry executives.

Gene therapies aim to correct certain diseases by replacing the missing or mutated version of a gene found in a patients cells with healthy copies. With the potential to cure devastating illnesses in a single dose, drugmakers say they justify prices well above $1 million per patient.

But the treatments are also extremely complex to make, involving the cultivation of living material, and still pose a risk of serious side effects.

Drugmakers say building their own manufacturing plants is a response to rising costs and delays associated with relying on third-party contract manufacturers, which are also expanding to capitalize on demand.

They say owning their own facilities helps safeguard proprietary production methods and more effectively address any concerns raised by the U.S. Food and Drug Administration (FDA), which is keeping a close eye on manufacturing standards.

Theres so little capacity and capability at contract manufacturers for the novel gene therapy processes being developed by companies, said David Lennon, president of AveXis, Novartiss gene therapy division. We need internal manufacturing capabilities in the long term.

SEE ALSO:

The Medicines Manufacturing Innovation Centre to be built in Scotland

Ricoh: The advantages of 3D printing across the healthcare sector

AstraZeneca experiences significant sales growth due to introduction of new drugs

Read the latest issue of Manufacturing Global here

Pushing the Limits

The approach is not without risks. The rewards are potentially great, however.

Gene therapy is one of the hottest areas of drug research and, given the life-changing possibilities, the FDA is helping to speed treatments to market.

It has approved two so far, including Novartiss Zolgensma treatment for a rare muscular disorder priced at $2 million, and expects 40 new gene therapies to reach the U.S. market by 2022.

There are currently several hundred under development by around 30 drugmakers for conditions from hemophilia to Duchenne muscular dystrophy and sickle cell anemia. The proliferation of these treatments is pushing the limits of the industrys existing manufacturing capacity.

Developers of gene therapies that need to outsource manufacturing face wait times of about 18 months to get a production slot, company executives told Reuters. They are also charged fees to reserve space that run into millions of dollars, more than double the cost of a few years ago, according to gene therapy developer RegenxBio.

As a result, companies including bluebird bio, PTC Therapeutics and Krystal Biotech are also investing in gene therapy manufacturing, according to a Reuters analysis of public filings and executive interviews.

They follow Biomarin Pharmaceutical Inc, developer of a gene therapy for hemophilia, which constructed one of the industrys largest manufacturing facilities in 2017. The FDA is keeping a close eye on standards.

Regulatory Scrutiny

This comes amid the agencys disclosure in August that it is investigating alleged data manipulation by former executives at Novartis AveXis unit.

AveXis had switched its method for measuring Zolgensmas potency in animal studies. When results using the new method didnt meet expectations, the executives allegedly altered the data to cover it up, the FDA and Novartis have said.One of the former executives, Brian Kaspar, denied wrongdoing in a statement to Reuters. Another, his brother Allan Kaspar, could not be reached for comment.

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Pfizer and Novartis lead $2bn spending on gene therapy production - Manufacturing Global

NEW YORK, Nov. 28, 2019 /PRNewswire/ --

INTRODUCTIONOver the last 12 months, the pharmaceutical industry reported a year-on-year increment of nearly 75% in funding to support the development of various cell and gene therapies. In fact, close to USD 5 billion has been invested into research on gene-based therapies in the previous two decades. Interestingly, over 2,600 clinical studies have been initiated in this field of research, since 1989. The aforementioned numbers are indicative of the rapid pace of development in this upcoming segment of the biopharmaceutical industry. The development of such therapy products require gene delivery vehicles, called vectors, to desired locations within the body (in vivo) / specific cells (ex vivo). The growing demand for such therapies and the rising number of clinical research initiatives in this domain has led to an increase in demand for preclinical and clinical grade gene delivery vectors. Fundamentally, genetic modifications can be carried out using either viral (such as adenovirus, adeno associated virus (AAV), lentivirus, retrovirus, Sendai virus, herpes simplex virus, vaccinia virus, baculovirus and alphavirus) or non-viral (such as plasmid DNA) vectors. Moreover, recent advances in vector research have led to the development of several innovative viral / non-viral gene delivery approaches.

Read the full report: https://www.reportlinker.com/p05828868/?utm_source=PRN

At present, 10+ genetically modified therapies have received approval / conditional approval in various regions of the world; these include (in the reverse chronological order of year of approval) Zynteglo (2019), Zolgensma (2019), Collategene (2019), LUXTURNA (2017), YESCARTA (2017), Kymriah (2017), INVOSSA (2017), Zalmoxis (2016), Strimvelis (2016), Imlygic (2015), Neovasculagen (2011), Rexin-G (2007), Oncorine (2005) and Gendicine (2003). In addition, over 500 therapy candidates are being investigated across different stages of development. The growing number of gene-based therapies, coupled to their rapid progression through the drug development process, has created significant opportunities for companies with expertise in vector manufacturing. Presently, a number of industry (including both well-established companies and smaller R&D-focused initiatives), and non-industry players (academic institutes) claim to be capable of manufacturing different types of viral and non-viral vectors. In addition, there are several players offering novel technology solutions, which are capable of improving existing genetically modified therapy products and upgrading their affiliated manufacturing processes. Considering prevalent and anticipated future trends, we believe that the vector and gene therapy manufacturing market is poised to grow steadily, driven by a robust pipeline of therapy candidates and technical advances aimed at mitigating existing challenges related to gene delivery vector and advanced therapy medicinal products.

SCOPE OF THE REPORTThe "Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (3rd Edition), 2019-2030 (Focus on AAV, Adenoviral, Lentiviral, Retroviral, Plasmid DNA and Other Vectors)" report features an extensive study of the rapidly growing market of viral and non-viral vector and gene therapy manufacturing, focusing on contract manufacturers, as well as companies with in-house manufacturing facilities. The study presents an in-depth analysis of the various firms / organizations that are engaged in this domain, across different regions of the globe. Amongst other elements, the report includes: An overview of the current status of the market with respect to the players involved (both industry and non-indutry) in manufacturing viral vectors, non-viral vectors and other novel types of vectors. It features information on the year of establishment, scale of production, type of vectors manufactured, location of manufacturing facilities, applications of vectors (in gene therapy, cell therapy, vaccines and others), and purpose of production (fulfilling in-house requirements / for contract services). An informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies; the analysis also takes into consideration various relevant parameters, such as target patient population, dosing frequency and dose strength. An estimate of the overall, installed vector manufacturing capacity of industry players based on information available in the public domain, and insights generated via both secondary and primary research. The analysis also highlights the distribution of the global capacity by vector type (viral vector and plasmid DNA), scale of operation (clinical and commercial), size of the company / organization (small-sized, mid-sized and large) and key geographical regions (North America, Europe, Asia Pacific and the rest of the world). An in-depth analysis of viral vector and plasmid DNA manufacturers, featuring three schematic representations; namely [A] a three dimensional grid analysis, representing the distribution of vector manufacturers (on the basis of type of vector) across various scales of operation and purpose of production (in-house operations and contract manufacturing services), [B] a logo landscape of viral vector and plasmid DNA manufacturers based on the type (industry and non-industry) and the size of the industry player (small-sized, mid-sized and large companies), and [C] a schematic world map representation, highlighting the geographical locations of vector manufacturing hubs. An analysis of recent collaborations and partnership agreements inked in this domain since 2015; it includes details of deals that were / are focused on the manufacturing of vectors, whihc were analyzed on the basis of year of agreement, type of agreement, type of vector involved, and scale of operation (laboratory, clinical and commercial). An analysis of the various factors that are likely to influence the pricing of vectors, featuring different models / approaches that may be adopted by product developers / manufacturers in order to decide the prices of proprietary vectors. An overview of other viral / non-viral gene delivery approaches that are currently being researched for the development of therapies involving genetic modification. Elaborate profiles of key players based in North America, Europe and Asia-Pacific (shortlisted based on scale of operation). Each profile features an overview of the company / organization, its financial performance (if available), information on its manufacturing facilities, vector manufacturing technology and an informed future outlook. A discussion on the factors driving the market and the various challenges associated with the vector production process.

One of the key objectives of this report was to evaluate the current market size and the future opportunity associated with the vector manufacturing market, over the coming decade. Based on various parameters, such as the likely increase in number of clinical studies, anticipated growth in target patient population, existing price variations across different vector types, and the anticipated success of gene therapy products (considering both approved and late-stage clinical candidates), we have provided an informed estimate of the likely evolution of the market in the short to mid-term and long term, for the period 2019-2030. In order to provide a detailed future outlook, our projections have been segmented on the basis of [A] type of vectors (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), [B] applications (gene therapy, cell therapy and vaccines), [C] therapeutic area (oncological disorders, inflammation & immunological diseases, neurological disorders, ophthalmic disorders, muscle disorders, metabolic disorders, cardiovascular disorders and others), [D] scale of operation (preclinical, clinical and commercial) and [E] geography (North America, Europe, Asia Pacific and rest of the world).

The research, analysis and insights presented in this report are backed by a deep understanding of key insights generated from both secondary and primary research. For the purpose of the study, we invited over 160 stakeholders to participate in a survey to solicit their opinions on upcoming opportunities and challenges that must be considered for a more inclusive growth. Our opinions and insights presented in this study were influenced by discussions held with several key players in this domain. The report features detailed transcripts of interviews held with the stakeholders: Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences) Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals) Jeffrey Hung (Chief Commercial Officer, Vigene Biosciences) Olivier Boisteau, (Co-Founder / President, Clean Cells), Laurent Ciavatti (Business Development Manager, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells) Joost van den Berg (Director, Amsterdam BioTherapeutics Unit) Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital) Colin Lee Novick (Managing Director, CJ Partners) Cedric Szpirer (Executive & Scientific Director, Delphi Genetics) Semyon Rubinchik (Scientific Director, ACGT) Alain Lamproye (President of Biopharma Business Unit, Novasep) Astrid Brammer (Senior Manager Business Development, Richter-Helm) Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing) Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Marketing Manager, Plasmid Factory) Nicolas Grandchamp (R&D Leader, GEG Tech)

All actual figures have been sourced and analyzed from publicly available information forums and primary research discussions. Financial figures mentioned in this report are in USD, unless otherwise specified.

RESEARCH METHODOLOGYThe data presented in this report has been gathered via secondary and primary research. For all our projects, we conduct interviews with experts in the area (academia, industry, medical practice and other associations) to solicit their opinions on emerging trends in the market. This is primarily useful for us to draw out our own opinion on how the market may evolve across different regions and technology segments. Wherever possible, the available data has been checked for accuracy from multiple sources of information.

The secondary sources of information include: Annual reports Investor presentations SEC filings Industry databases News releases from company websites Government policy documents Industry analysts' views

While the focus has been on forecasting the market over the period 2019-2030, the report also provides our independent view on various technological and non-commercial trends emerging in the industry. This opinion is solely based on our knowledge, research and understanding of the relevant market gathered from various secondary and primary sources of information.

CHAPTER OUTLINESChapter 2 is an executive summary of the insights captured in our research. The summary offers a high-level view on the likely evolution of the vector and gene therapy manufacturing market in the short to mid-term, and long term.

Chapter 3 is a general introduction to the various types of viral and non-viral vectors. It includes a detailed discussion on the design, manufacturing requirements, advantages, limitations and applications of currently available gene delivery vehicles. The chapter also provides a brief description of the clinical and approved pipeline of genetically modified therapies. Further, it includes a review of the latest trends and innovations in the contemporary vector manufacturing market.

Chapter 4 provides a detailed overview of around 80 companies, featuring both contract service providers and in-house manufacturers that are actively involved in the production of viral vectors and / or gene therapies utilizing viral vectors. The chapter provides details on the year of establishment, scale of production, type of viral vectors manufactured (AAV, adenoviral, lentiviral, retroviral and others), location of manufacturing facilities, applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of production (fulfilling in-house requirements / for contract services).

Chapter 5 provides an overview of around 30 industry players that are actively involved in the production of plasmid DNA and other non-viral vectors and / or gene therapies utilizing non-viral vectors. The chapter provides details on the year of establishment, scale of production, location of manufacturing facilities, applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of vector production (fulfilling in-house requirements / for contract services).

Chapter 6 provides an overview of around 80 non-industry players (academia and research institutes) that are actively involved in the production of vectors (both viral and non-viral) and / or gene therapies. The chapter provides details on the year of establishment, scale of production, location of manufacturing facilities, type of vectors manufactured (AAV, adenoviral, lentiviral, retroviral, plasmid DNA and others), applications of vectors (gene therapies, cell therapies, vaccines and others) and purpose of vector production (fulfilling in-house requirements / for contract services).

Chapter 7 features detailed profiles of the US based contract service providers / in-house manufacturers that possess commercial scale capacities for the production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience and an informed future outlook.

Chapter 8 features detailed profiles of EU based contract service providers / in-house manufacturers that possess commercial scale capacities for the production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience, and an informed future outlook.

Chapter 9 features detailed profiles of Asia-Pacific based contract service provider(s) / in-house manufacturer(s) that possess commercial scale capacities for production of viral vectors / plasmid DNA. Each profile presents a brief overview of the company, its financial information (if available), details on vector manufacturing facilities, manufacturing experience, and an informed future outlook.

Chapter 10 provides detailed information on other viral / non-viral vectors (including alphavirus vectors, Bifidobacterium longum vectors, Listeria monocytogenes vectors, myxoma virus based vectors, Sendai virus based vectors, self-complementary vectors (improved versions of AAV), and minicircle DNA and Sleeping Beauty transposon vectors (non-viral gene delivery approach)) that are currently being utilized by pharmaceutical players to develop gene therapies, T-cell therapies and certain vaccines, as well. This chapter presents overview on all the aforementioned types of vectors, along with examples of companies that use them in their proprietary products. It also includes examples of companies that are utilizing specific technology platforms for the development / manufacturing of some of these novel vectors.

Chapter 11 features an elaborate analysis and discussion of the various collaborations and partnerships related to the manufacturing of vectors or gene therapies, which have been inked amongst players. It includes a brief description of the purpose of the partnership models (including licensing agreements, mergers / acquisitions, product development, service alliances, manufacturing, and others) that have been adopted by the stakeholders in this domain, since 2015. It consists of a schematic representation showcasing the players that have forged the maximum number of alliances. Furthermore, we have provided a world map representation of the deals inked in this field, highlighting those that have been established within and across different continents.

Chapter 12 presents a collection of key insights derived from the study. It includes a grid analysis, highlighting the distribution of viral vectors and plasmid DNA manufacturers on the basis of their scale of production and purpose of manufacturing (fulfilling in-house requirement / contract service provider). In addition, it consists of a logo landscape, representing the distribution of viral vector and plasmid DNA manufacturers based on the type of organization (industry / non-industry) and size of employee base. The chapter also consists of six world map representations of manufacturers of viral / non-viral vectors (lentiviral, adenoviral, AAV and retroviral vectors, and plasmid DNA), depicting the most active geographies in terms of the presence of the organizations. Furthermore, we have provided a schematic world map representation to highlight the locations of global vector manufacturing hubs across different continents.

Chapter 13 highlights our views on the various factors that may be taken into consideration while pricing viral vectors / plasmid DNA. It features discussions on different pricing models / approaches that manufacturers may choose to adopt to decide the prices of their proprietary products.

Chapter 14 features an informed estimate of the annual demand for viral and non-viral vectors, taking into account the marketed gene-based therapies and clinical studies evaluating vector-based therapies. This section offers an opinion on the required scale of supply (in terms of vector manufacturing services) in this market. For the purpose of estimating the current clinical demand, we considered the active clinical studies of different types of vector-based therapies that have been registered till date. The data was analysed on the basis of various parameters, such as number of annual clinical doses, trial location, and the enrolled patient population across different geographies. Further, in order to estimate the commercial demand, we considered the marketed vector-based therapies, based on various parameters, such as target patient population, dosing frequency and dose strength.

Chapter 15 features an informed analysis of the overall installed capacity of the vectors and gene therapy manufacturers. The analysis is based on meticulously collected data (via both secondary and primary research) on reported capacities of various small-sized, mid-sized and large companies, distributed across their respective facilities. The results of this analysis were used to establish an informed opinion on the vector production capabilities of the organizations across different types of vectors (viral vectors, plasmid DNA, and both), scale of operation (clinical and commercial) and geographies (North America, EU, Asia-Pacific and the rest of the world).

Chapter 16 presents a comprehensive market forecast analysis, highlighting the likely growth of vector and gene therapy manufacturing market till the year 2030. We have segmented the financial opportunity on the basis of [A] type of vectors (AAV vector, adenoviral vector, lentiviral vector, retroviral vector, plasmid DNA and others), [B] applications (gene therapy, cell therapy and vaccines), [C] therapeutic area (oncological disorders, inflammation & immunological diseases, neurological disorders, ophthalmic disorders, muscle disorders, metabolic disorders, cardiovascular disorders and others), [D] scale of operation (preclinical, clinical and commercial) and [E] geography (North America, Europe, Asia Pacific and rest of the world). Due to the uncertain nature of the market, we have presented three different growth tracks outlined as the conservative, base and optimistic scenarios.

Chapter 17 provides details on the various factors associated with popular viral vectors and plasmid DNA that act as market drivers and the various challenges associated with the production process. This information has been validated by soliciting the opinions of several industry stakeholders active in this domain.

Chapter 18 presents insights from the survey conducted on over 160 stakeholders involved in the development of different types of gene therapy vectors. The participants, who were primarily Director / CXO level representatives of their respective companies, helped us develop a deeper understanding on the nature of their services and the associated commercial potential.

Chapter 19 summarizes the entire report. The chapter presents a list of key takeaways and offers our independent opinion on the current market scenario and evolutionary trends that are likely to determine the future of this segment of the industry.

Chapter 20 is a collection of transcripts of the interviews conducted with representatives from renowned organizations that are engaged in the vector and gene therapy manufacturing domain. In this study, we spoke to Menzo Havenga (Chief Executive Officer and President, Batavia Biosciences), Nicole Faust (Chief Executive Officer & Chief Scientific Officer, CEVEC Pharmaceuticals), Jeffrey Hung (Chief Commercial Officer, Vigene Biosciences), Olivier Boisteau, (Co-Founder / President, Clean Cells) and Xavier Leclerc (Head of Gene Therapy, Clean Cells), Laurent Ciavatti (Business Development Manager, Clean Cells), Joost van den Berg (Director, Amsterdam BioTherapeutics Unit), Bakhos A Tannous (Director, MGH Viral Vector Development Facility, Massachusetts General Hospital), Colin Lee Novick (Managing Director, CJ Partners), Cedric Szpirer (Executive & Scientific Director, Delphi Genetics), Semyon Rubinchik (Scientific Director, ACGT), Alain Lamproye (President of Biopharma Business Unit, Novasep), Astrid Brammer (Senior Manager Business Development, Richter-Helm), Brain M Dattilo (Business Development Manager, Waisman Biomanufacturing), Marco Schmeer (Project Manager, Plasmid Factory) and Tatjana Buchholz (Marketing Manager, Plasmid Factory), and Nicolas Grandchamp (R&D Leader, GEG Tech).

Chapter 21 is an appendix, which provides tabulated data and numbers for all the figures in the report.

Chapter 22 is an appendix that provides the list of companies and organizations that have been mentioned in the report.

Read the full report: https://www.reportlinker.com/p05828868/?utm_source=PRN

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Viral Vectors, Non-Viral Vectors and Gene Therapy Manufacturing Market (3rd Edition), 2019-2030 (Focus on AAV, Adenoviral, Lentiviral, Retroviral,...

UK cell and gene therapy firms are worried a shortage of skilled manufacturing staff will slow growth with some concerned Brexit will exacerbate the problem.

The findings come from a new skills survey by the Cell and Gene Therapy Catapult (CGTC) an organisation set up to support the sector by non-departmental government body, Innovate UK.

Of the 41 companies that responded, 98% said they planned to expand their headcount over the next five years. Of these, 83% raised concerns that hiring and retaining skilled staff will be an issue for growth.

Image: iStock/philhol

In addition, some respondents were concerned that Brexit will have a negative impact on recruiting and retaining skilled non-UK EU people according to the report.

More than 1,700 people are employed in bioprocessing roles in the UK cell and gene therapy sector, which is up from the 500 or so working in such positions in 2017. Based on this growth rate the CGTC expects 3,800 people will be working in such roles by 2024.

The survey also revealed 492 people are employed in cell and gene therapy manufacturing roles in the UK. This is expected to increase to 1,456 people up 196% by 2024. Respondents said finding staff with manufacturing skills as a substantial concern.

To address this, the report authors suggested cell and gene therapy firms would need to look beyond the sector.

The lack of talent will highly likely act as a brake to growth, with significant negative consequences on both organic and inward investment.

It is recommended, that companies are supported to deliver on their growth strategies, through the provision of supportive schemes, to both upskill their existing workforce as well as recruiting new talent, from outside of the sector.

The survey did not tally the number of EU nationals working in the UK cell and gene therapy sector or look at the potential impact Brexit would have on sectors ability to recruit.

However, a CGTC spokesperson told us We are confident that the UK cell and gene therapy industry will be able to source the necessary skills, and that the opportunities in research and training will remain attractive.

The spokesperson suggested overseas scientists continue to view the UK as attractive, adding We continue to see skilled people wanting to work in the UK sector from across the globe.

In addition, the spokesperson also expressed confidence cell and gene therapy developers would continue to see the UK as an attractive development and production base post withdrawal.

The supply chains for these advanced therapies are highly specialised and have been stringently developed in collaboration with medicine regulators to minimise any potential disruption.

There are already a number of advance therapies manufactured in the UK and exported seamlessly to the US for clinical trials and vice versa, we are confident that the movement of these therapies will remain unimpeded.

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Lack of UK cell and gene therapy skills a concern - Bioprocess Insider - BioProcess Insider

(Reuters) - Blackstone Group Inc (BX.N) said on Monday it will invest $400 million in a joint venture with Swiss drug company Ferring that is working on an experimental gene therapy for bladder cancer, the private equity giants largest ever bet on drug development.

FILE PHOTO: The ticker and trading information for Blackstone Group is displayed at the post where it is traded on the floor of the New York Stock Exchange (NYSE) April 4, 2016. REUTERS/Brendan McDermid

Investing in yet-to-be-approved medicines is a lucrative but also risky proposition for buyout firms, and only few have had the stomach to place such bets. Blackstone made its foray in the sector last year, acquiring Clarus, an investment firm specializing in life sciences.

For its part, Ferring will invest $170 million in the joint venture with Blackstone, dubbed FerGene, bringing its total funding to $570 million, the companies said in a statement.

FerGene is developing a gene therapy for bladder cancer patients with an aggressive form of the disease whose current options include having their bladder removed. The treatment works by entering the walls of the bladder where it releases a gene to trigger the patients own body to make a protein to fight off cancer.

We believe, and Ferring also believes, that this can change the standard of care in bladder cancer, a terrible disease, Nicholas Galakatos, senior managing director of Blackstone Life Sciences, said in an interview.

Oncology is a new area for Ferring, but it is one that we as Blackstone Life Sciences have a lot of experience in

The team assembled by Blackstone has worked at several of the worlds largest cancer drugmakers, including Roche unit Genentech, Merck & Co Inc (MRK.N), and Millennium Pharmaceuticals, now a part of Takeda Pharmaceutical Co Ltd (4502.T).

To minimize its risk, Blackstone invests in the late stages of drug development, when a medicine has already gone through important milestones. Late-stage drug development can also be expensive because of the clinical trials involved, something that Blackstone is seeking to capitalize on by partnering with pharmaceutical firms looking to share the cost burden.

FerGenes therapy, named nadofaragene firadenovec, is currently in the final stage of clinical research, results from which will be presented on Dec. 5 at the Society of Urologic Oncologys annual meeting.

Since it launched its life sciences unit, Blackstone has also formed a new company with Novartis AG (NOVN.S) to study a type of heart drug. Blackstone invested $250 million in that venture.

Reporting by Rebecca Spalding in New York; Editing by Alistair Bell

Original post:
Blackstone to invest $400 million in gene therapy venture with Ferring - Reuters

A research scientist at a laboratory of a pharmaceutical company in US. Reuters

The full scope of Novartis $500 million plan, revealed to Reuters in an interview with the companys gene therapy chief, has not been previously disclosed. It is second only to Pfizer, which has allocated $600 million to build its own gene therapy manufacturing plants, according to filings and interviews with industry executives.

Gene therapies aim to correct certain diseases by replacing the missing or mutated version of a gene found in a patients cells with healthy copies. With the potential to cure devastating illnesses in a single dose, drugmakers say they justify prices well above $1 million per patient.

But the treatments are also extremely complex to make, involving the cultivation of living material, and still pose a risk of serious side effects.

Drugmakers say building their own manufacturing plants is a response to rising costs and delays associated with relying on third-party contract manufacturers, which are also expanding to capitalise on demand. They say owning their own facilities helps safeguard proprietary production methods and more effectively address any concerns raised by the US Food and Drug Administration (FDA), which is keeping a close eye on manufacturing standards.

Theres so little capacity and capability at contract manufacturers for the novel gene therapy processes being developed by companies, said David Lennon, president of AveXis, Novartiss gene therapy division. We need internal manufacturing capabilities in the long term.

The approach is not without risks.

Bob Smith, senior vice president of Pfizers global gene therapy business, acknowledged drugmakers take a leap of faith when they make big capital investment outlays for treatments before they have been approved or, in some cases, even produced data demonstrating a benefit.

The rewards are potentially great, however.

Gene therapy is one of the hottest areas of drug research and, given the life-changing possibilities, the FDA is helping to speed treatments to market.

It has approved two so far, including Novartiss Zolgensma treatment for a rare muscular disorder priced at $2 million, and expects 40 new gene therapies to reach the US market by 2022.

There are currently several hundred under development by around 30 drugmakers for conditions from hemophilia to Duchenne muscular dystrophy and sickle cell anemia.

The proliferation of these treatments is pushing the limits of the industrys existing manufacturing capacity.

Developers of gene therapies that need to outsource manufacturing face wait times of about 18 months to get a production slot, company executives told Reuters.

They are also charged fees to reserve space that run into millions of dollars, more than double the cost of a few years ago, according to gene therapy developer RegenxBio.

As a result, companies including bluebird bio, PTC Therapeutics and Krystal Biotech are also investing in gene therapy manufacturing, according to a Reuters analysis of public filings and executive interviews.

They follow Biomarin Pharmaceutical, developer of a gene therapy for hemophilia, which constructed one of the industrys largest manufacturing facilities in 2017. The FDA is keeping a close eye on standards.

This comes amid the agencys disclosure in August that it is investigating alleged data manipulation by former executives at Novartis AveXis unit.

AveXis had switched its method for measuring Zolgensmas potency in animal studies. When results using the new method didnt meet expectations, the executives allegedly altered the data to cover it up, the FDA and Novartis have said.

One of the former executives, Brian Kaspar, denied wrongdoing in a statement to Reuters. Another, his brother Allan Kaspar, could not be reached for comment.

Novartis and the FDA say human clinical trials, which found Zolgensma effective in treating the most severe form of spinal muscular atrophy in infants, were not affected. Novartis also says its investments in gene therapy production started long before it became aware of the data manipulation allegations.

Reuters

Originally posted here:
Pfizer and Novartis lead pharma spending spree on gene therapy - Gulf Today

Lonza and DiNAQOR AG, a global gene therapy platform company, have formed a collaboration to advance DiNAQORs preclinical programs for the treatment of cardiac myosin-binding protein-C (MYBPC3) cardiomyopathies, a genetic condition that can result in heart failure.Lonza will provide DiMAQOR preclinical, clinical and commercial production support for the companys lead preclinical program DiNA-001, an adeno-associated virus (AAV) gene therapy program for patients with MYBPC3-linked cardiomyopathy. Lonzas cell-and-gene-therapy manufacturing facility in Houston, TX will handle all product supply for DiNA-001.Through this partnership, DiNAQOR will be able to leverage Lonza's extensive, dedicated teams and laboratories for viral-vector process-development, located in Houston.In addition to its cardiac gene therapy platform, DiNAQOR is also developing a local-regional delivery system for the heart. This will allow the company to route gene therapy directly to the cardiac muscle maximizing biodistribution and transduction of the cardiomyocytes. This approach will look to minimize potential adverse effects of systemic gene therapy delivery.DiNAQOR has established an innovative gene therapy platform that will allow for the evaluation of this promising treatment for monogenic cardiomyopathies, said Alberto Santagostino, senior vice president, head of cell and gene technologies, Lonza Pharma & Biotech. DiNAQOR represents the truly trailblazing companies that we strive to empower in the cell and gene therapy space and we are fully committed to the DiNAQOR team as they seek to advance novel treatment options for people living with heart disease.Johannes Holzmeister, chairman and chief executive officer, DiNAQOR, said, Lonza is a leader in the manufacturing of adeno-associated virus gene therapy vectors and is the optimal partner to help us rapidly advance and scale the production of DiNA-001 from early-stage clinical trials through commercialization. Precise and rapid genetic diagnostics, leading analytics, and an adequate product supply for all stages of clinical development and commercialization are necessary to bring these potentially transformational gene therapies to patients suffering from heart failure. We are excited to collaborate with Lonza on this critical initiative.

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Lonza And DiNAQOR AG Enter Gene Therapy Collaboration - Contract Pharma

DetailsCategory: More NewsPublished on Wednesday, 27 November 2019 13:20Hits: 926

Collaboration will Target a Therapeutic Approach for Treating Asthma and Allergic Diseases

NEW YORK, NY, USA I November 26, 2019 I Hoth Therapeutics, Inc. (Nasdaq: HOTH) ("HOTH" or the "Company"), a biopharmaceutical company focused on developing new generation therapies for dermatological disorders such as atopic dermatitis, chronic wounds, psoriasis and acne, today announced it has entered into a licensing agreement with North Carolina State University (NC State) to study NC State's Exon Skipping Approach for Treating Allergic Diseases.

This Exon Skipping Approach was developed by Dr. Glenn Cruse, Principal Investigator and Assistant Professor in the Department of Molecular Biomedical Sciences at the NC State College of Veterinary Medicine. During Dr. Cruse's research, a new approach for the technique of antisense oligonucleotide-mediated exon skipping to specifically target and down-regulate IgE receptor expression in mast cells was identified. These findings set a breakthrough for allergic diseases as they are driven by the activation of mast cells and the release of mediators in response to IgE-directed antigens.

Mr. Robb Knie, Chief Executive Officer of Hoth, commented, "This new collaboration will allow us to leverage this invention from the renowned expertise of Dr. Glenn Cruse and his scientific team at North Carolina State University. We look forward to seeing how their work advances and what this might mean for patients suffering from undesirable steroid side effects who need an alternate treatment for asthma and other allergic diseases."

The high-affinity IgEreceptor (FcRI) plays a central role in the initiation ofallergic responses. The research project looks to target novel genes, which are critical for surface IgE receptor expression. The project will utilize splice-switching oligonucleotides (SSOs) to force expression of a truncated isoform of the target genes to reduce expression ofFcRIin mouse asthma models.

Through this collaborative project, NCSU looks to establish the most effective approach for targeting genes that regulate surface expression of FcRI in mast cells that mediate allergic airway inflammation. The study will be administering SSOs for the target genes, to optimize delivery and examine the best therapeutic approach.

About Hoth Therapeutics, Inc.Hoth Therapeutics, Inc. isa clinical-stage biopharmaceutical company focused on developing new generation therapies for dermatological disorders. HOTH's pipeline has the potential to improve the quality of life for patients suffering from indications including atopic dermatitis, chronic wounds, psoriasis, and acne. HOTH has the exclusive worldwide rights to BioLexa, the company's proprietary lead drug candidate topical platform that uniquely combines two FDA approved compounds to fight bacterial infections across multiple indications. HOTH is preparing to launch its clinical trial for the treatment of adolescent subjects, 2-17 years of age, with mild to moderate atopic dermatitis during 2020. To learn more, please visitwww.hoththerapeutics.com.

SOURCE: Hoth Therapeutics

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Expansions of DNA repeats are very hard to analyze. A method developed by researchers at the Max Planck Institute for Molecular Genetics in Berlin allows for a detailed look at these previously inaccessible regions of the genome. It combines nanopore sequencing, stem cell, and CRISPR-Cas technologies. The method could improve the diagnosis of various congenital diseases and cancers in the future.

Large parts of the genome consist of monotonous regions where short sections of the genome repeat hundreds or thousands of times. But expansions of these "DNA repeats" in the wrong places can have dramatic consequences, like in patients with Fragile X syndrome, one of the most commonly identifiable hereditary causes of cognitive disability in humans. However, these repetitive regions are still regarded as an unknown territory that cannot be examined appropriately, even with modern methods.

A research team led by Franz-Josef Mller at the Max Planck Institute for Molecular Genetics in Berlin and the University Hospital of Schleswig-Holstein in Kiel recently shed light on this inaccessible region of the genome. Mller's team was the first to successfully determine the length of genomic tandem repeats in patient-derived stem cell cultures. The researchers additionally obtained data on the epigenetic state of the repeats by scanning individual DNA molecules. The method, which is based on nanopore sequencing and CRISPR-Cas technologies, opens the door for research into repetitive genomic regions, and the rapid and accurate diagnosis of a range of diseases.A gene defect on the X chromosomeIn Fragile X syndrome, a repeat sequence has expanded in a gene called FMR1 on the X chromosome. "The cell recognizes the repetitive region and switches it off by attaching methyl groups to the DNA," says Mller. These small chemical changes have an epigenetic effect because they leave the underlying genetic information intact. "Unfortunately, the epigenetic marks spread over to the entire gene, which is then completely shut down," explains Mller. The gene is known to be essential for normal brain development. He states: "Without the FMR1 gene, we see severe delays in development leading to varying degrees of intellectual disability or autism."

Female individuals are, in most cases, less affected by the disease, since the repeat region is usually located on only one of the two X chromosomes. Since the unchanged second copy of the gene is not epigenetically altered, it is able to compensate for the genetic defect. In contrast, males have only one X chromosome and one copy of the affected gene and display the full range of clinical symptoms. The syndrome is one of about 30 diseases that are caused by expanding short tandem repeats.

First precise mapping of short tandem repeats

In this study, Mller and his team investigated the genome of stem cells that were derived from patient tissue. They were able to determine the length of the repeat regions and their epigenetic signature, a feat that had not been possible with conventional sequencing methods. The researchers also discovered that the length of the repetitive region could vary to a large degree, even among the cells of a single patient.

The researchers also tested their process with cells derived from patients that contained an expanded repeat in one of the two copies of the C9orf72 gene. This mutation leads to one of the most common monogenic causes of frontotemporal dementia and amyotrophic lateral sclerosis. "We were the first to map the entire epigenetics of extended and unchanged repeat regions in a single experiment," says Mller. Furthermore, the region of interest on the DNA molecule remained physically wholly unaltered. "We developed a unique method for the analysis of single molecules and for the darkest regions of our genome - that's what makes this so exciting for me."

Tiny pores scan single molecules

"Conventional methods are limited when it comes to highly repetitive DNA sequences. Not to mention the inability to simultaneously detect the epigenetic properties of repeats," says Bjrn Brndl, one of the first authors of the publication. That's why the scientists used Nanopore sequencing technology, which is capable of analyzing these regions. The DNA is fragmented, and each strand is threaded through one of a hundred tiny holes ("nanopores") on a silicon chip. At the same time, electrically charged particles flow through the pores and generate a current. When a DNA molecule moves through one of these pores, the current varies depending on the chemical properties of the DNA. These fluctuations of the electrical signal are enough for the computer to reconstruct the genetic sequence and the epigenetic chemical labels. This process takes place at each pore and, thus, each strand of DNA.

Genome editing tools and bioinformatics illuminate "dark matter"Conventional sequencing methods analyze the entire genome of a patient. Now, the scientists designed a process to look at specific regions selectively. Brndl used the CRISPR-Cas system to cut DNA segments from the genome that contained the repeat region. These segments went through a few intermediate processing steps and were then funneled into the pores on the sequencing chip.

"If we had not pre-sorted the molecules in this way, their signal would have been drowned in the noise of the rest of the genome," says bioinformatician Pay Giesselmann. He had to develop an algorithm specifically for the interpretation of the electrical signals generated by the repeats: "Most algorithms fail because they do not expect the regular patterns of repetitive sequences." While Giesselmann's program "STRique" does not determine the genetic sequence itself, it counts the number of sequence repetitions with high precision. The program is freely available on the internet.

Numerous potential applications in research and the clinic"With the CRISPR-Cas system and our algorithms, we can scrutinize any section of the genome - especially those regions that are particularly difficult to examine using conventional methods," says Mller, who is heading the project. "We created the tools that enable every researcher to explore the dark matter of the genome," says Mller. He sees great potential for basic research. "There is evidence that the repeats grow during the development of the nervous system, and we would like to take a closer look at this."

The physician also envisions numerous applications in clinical diagnostics. After all, repetitive regions are involved in the development of cancer, and the new method is relatively inexpensive and fast. Mller is determined to take the procedure to the next level: "We are very close to clinical application."

Reference: Giesselmann et al. 2019.Analysis of short tandem repeat expansions and their methylation state with nanopore sequencing. Nature Biotechnology.DOI: https://doi.org/10.1038/s41587-019-0293-x.

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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New Device Permits a Closer Look at Previously Inaccessible Areas of the Genome - Technology Networks

Salmonella is acting up in Michigan, and it could be a model for whats happening in other states, according to a new Michigan State University study.

The study, appearing in Frontiers in Medicine, documents a substantial uptick in antibiotic resistant strains, and consequently, longer hospital stays as doctors work to treat the increasing virulent pathogens.

If you get a salmonella infection that is resistant to antibiotics today, you are more likely to be hospitalized longer, and it will take you longer to recover, said Shannon Manning, MSU Foundation professor in theDepartment of Microbiology and Molecular Genetics and senior author of the study. We need better detection methods at the clinical level to identify resistant pathogens earlier so we can treat them with the right drugs the first time.

Losing a day or more to misdiagnosis or improper treatment allows symptoms to get worse. Doctors might kill off a subpopulation of bacteria that are susceptible, but the ones that are resistant grow stronger, she added.

Salmonella is a diverse group of bacterial pathogens that causes foodborne infections. Infected patients often develop diarrhea, nausea, vomiting and abdominal pain, though some infections are more severe and can be life threatening.

When it comes to treatments, each strain reacts differently to the range of antibiotics available for prescription by doctors. So getting it right the first time is crucial.

Specifically in Michigan, doctors are seeing more strains that are resistant to ampicillin, a common antibiotic prescribed to treat salmonella. Multidrug resistance, or resistance to more than three classes of antibiotics, has also increased in Michigan and could further complicate patient treatment plans.

Were still uncertain as to why this is happening; it could be that these antibiotics have been overprescribed in human and veterinary medicine and that possessing genes for resistance has allowed these bacteria to grow and thrive in the presence of antibiotics, Manning said. Each state has its own antibiotic-resistance issues. Its important that the medical profession remains vigilant to ever-changing patterns of resistance in salmonella and other foodborne pathogens, rather than look for a blanket national solution.

Historically, salmonella has affected young children and the elderly, but now theres been a rise in adult cases, suggesting that the epidemiology of the infections has changed in Michigan.

Diving into individual strains of salmonella, the team of scientists found that patients with Typhimurium were more likely to have resistant infections as were patients infected during the fall, winter or spring months.

Another distinction was revealed between the strains affecting people living in rural and urban areas. Enteritis infections tend to be higher in rural areas. This may be attributed to rural residents exposure to farm animals or untreated sources of water.

Each states salmonella population has its own personality; so every states approach to identifying disease drivers and effective treatments should be modified to reflect these traits.

Our results show the importance of surveillance, monitoring resistance frequencies and identifying risk factors specific to each state and region, Manning said. The trends that are revealed can lead to new prevention strategies.

Additional MSU researchers contributing to the study include Sanjana Mukherjee, the lead author, Chase Anderson and Rebekah Mosci. Scientists from Wayne State, Sparrow Hospitals and the Michigan Department of Health and Human Services also contributed to this research.

(Note for media: Please include a link to the original paper in online coverage: https://www.frontiersin.org/articles/10.3389/fmed.2019.00250/full)

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The nature of salmonella is changing and it's meaner - MSUToday

Fifty-two faculty members and researchers at the University of California San Diego are among the worlds most influential in their fields. The Web of Science Group, an information and technology provider for the global scientific research community, compiled its2019 Highly Cited Researcherslist of more than 6,000 scientists from around the world whose studies were among the top 1% of most-cited publications in their field over the past 11 years.

The number of highly cited researchers from UC San Diego increased by 13% over last years number of forty-six. The listing covers 21 fields of study as well as a cross-field category for researchers who are widely cited across multiple fields. UC San Diego had researchers listed in 14 fields, with the most cited in cross-field (23), followed by molecular biology and genetics (5), clinical medicine (4) and social sciences (4).

UC San Diego has some of the most dedicated, brilliant and hard-working faculty and researchers in the world. Their inclusion on the list of highly cited researchers is a measure of their impact in their respective fields of study as they continue to advance the frontiers of knowledge, said Chancellor Pradeep K. Khosla.

Of particular note is Director for the Center of Microbiome Innovation Rob Knights inclusion in three separate areas of study (biology and biochemistry, environment and ecology, microbiology). Out of 6,216 highly cited researchers, only 11 were cited in three fields, making Knight part of a super elite 0.3% of those listed.

There were also 23 Nobel laureates on the list, one of whom, Roger Tsien, was a distinguished professor of both Pharmacology in the School of Medicine and of Chemistry and Biochemistry at UC San Diego until his death in 2016. He shared the Nobel Prize in Chemistry with two others in 2008 for discovering and developing green fluorescent protein.

David Pendlebury, Senior Citation Analyst at the Web of Science Groups Institute for Scientific Information said that the highly cited researchers create gains for society, innovation and knowledge that make the world healthier, richer, more sustainable and more secure.

It is especially encouraging to see not only the number of highly cited researchers at the university, but the broad range of fields in which they are cited. It really speaks to the fact that UC San Diego conducts groundbreaking research across a wide range of disciplines, said Vice Chancellor for Research Sandra A. Brown. I congratulate everyone on their excellent research and contributions.

The 52 UC San Diego faculty members named by Web of Science and the fields of study in which they were cited are:

Gregory Aarons,social sciences

Ludmil Alexandrov, molecular biology and genetics

David Brenner,cross-field

Kristin Cadenhead,psychiatry/psychology

Kelli Cain, social sciences

Shu Chien, cross-field

Don Cleveland,neuroscience and behavior

Seth Cohen,chemistry

Pieter Dorrestein,cross-field

Mark Ellisman, cross-field

Mark Estelle,plant and animal science

Michael Folger, cross-field

Anthony Gamst, cross-field

Christopher Glass,molecular biology and genetics

Uri Gneezy,economics and business

Antonio Gonzalez, microbiology

Kun-Liang Guan,molecular biology and genetics

Trey Ideker,cross-field

Michael Karin,molecular biology and genetics

Arthur Kavanaugh,clinical medicine

Dusan Keres, space science

Rob Knight,(listed in 3 fields) biology and biochemistry, environment and ecology, microbiology

Razelle Kurzrock, clinical medicine

Lisa Levin, cross-field

Irene Litvan, neuroscience and behavior

Rohit Loomba, clinical medicine

Prashant Mali, biology and biochemistry

Eliezer Masliah, cross-field

Victor Nizet, cross-field

Jerrold Olefsky,cross-field

Bernhard Palsson,biology and biochemistry

Veerabhadran Ramanathan,cross-field

Bing Ren,molecular biology and genetics

Jeremy Rich, cross-field

Douglas Richman,cross-field

Michael Sailor,cross-field

James Sallis,social sciences

William Sandborn,clinical medicine

Bernd Schnabl, cross-field

Julian Schroeder,plant and animal science

Terrence Sejnowski, cross-field

Claude Sirlin, cross-field

Murray Stein,psychiatry/psychology

Steffanie Strathdee, cross-field

Roger Tsien, cross-field

Ming Tsuang,psychiatry/psychology

Joseph Wang,chemistry

Shang-Ping Xie,geosciences

Gene Yeo, cross-field

Kun Zhang, cross-field

Liangfang Zhang,cross-field

Yunde Zhao, plant and animal science

Shu-Hong Zhu, social sciences

You can read about Web of Sciences methodology on their website.

UC San Diegos Studio Ten 300 offers radio and television connections for media interviews with our faculty. For more information, email .(JavaScript must be enabled to view this email address).

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52 UC San Diego Researchers Are Most Highly Cited in Their Fields - UC San Diego Health

A glance around the walls of Barry J. Byrnes office reveals a lot about the pediatric cardiologist who runs thePowell Gene Therapy Center at University of Florida (UF).

In one corner is an unusual painting by 9-year-old Will Barkowsky of Jacksonville, Fla. Will, the first boy with Duchenne muscular dystrophy to takeSarepta Therapeutics exon-skipping medication Exondys 51 (eteplirsen), put together his oil-on-canvas masterpiece using the tire tracks of his wheelchair, making sure the colors didnt mix.

Nearby is a movie poster for The Ataxian an award-winning 2015 documentary by Kevin Schlanser and Zack Bennett about 17-year-old Kyle Bryant, who despite having Friedreichs ataxia embarks on a cross-country bicycle trip with three buddies.

Another movie poster advertises Extraordinary Measures, the 2010 tearjerker starring Brendan Fraser as John Crowley the father of two kids with Pompe disease and later, the founder of Amicus Therapeutics and Harrison Ford as fictional researcher Robert Stonehill, who discovers a treatment for the genetic disorder that eventually saves the lives of Crowleys children.

Theres also a model of a Blalock-Taussig shunt frequently used in congenital heart surgery, as well as one of an adeno-associated virus (AAV) vector, along with a prominent photo of Byrne with Ron Bartek, co-founder and director of the Friedreichs Ataxia Research Alliance (FARA).

Friedreichs ataxia is where were putting most of our efforts now, said Byrne, who spoke to BioNews Services publisher of this website at length during a recent visit to his lab in Gainesville, Fla.

Byrne, along with Jerry Mendell, MD, a neurologist with Nationwide Childrens Hospital in Columbus, Ohio, hosted a Nov. 20 webinar on gene therapy organized by the National Organization for Rare Disorders (NORD) and the American Society for Gene & Cell Therapy.

The two experts were introduced by Katie Kowalski, senior program manager for NORDs Educational Initiatives. The webinar, Understanding the Gene Therapy Process and Aftercare, was the fourth in a five-part series underwritten by Amicus and Sarepta, as well as two other companies, Avrobio and Bluebird Bio.

The final webinar in the series, Life After Gene Therapy, is scheduled for Dec. 18.

Mendell, who heads Nationwides Center for Gene Therapy, specializes in gene therapy research for Duchenne as well as limb-girdle muscular dystrophy, spinal muscular atrophy (SMA) and X-linked myotubular myopathy. He was a principal investigator for the Novartis therapy Zolgensma, which uses an AAV vector to carry a working version of SMN1, the mutated gene in people with SMA.

Zolgensma won approval from the U.S. Food and Drug Administration (FDA) in May 2019 as the first gene therapy to treat SMA in infants up to 2 years of age.

At $2.125 million per patient, the hour-long Zolgensma infusion is the most expensive medicine in history. The cost easily eclipses that of the only other FDA-approved treatment for SMA, BiogensSpinraza(nusinersen), which retails for $750,000 the first year and $375,000 every year after.

Many of my colleagues have been trying to make inroads for years, Mendell said. When we first got into the gene therapy domain, we were limited by technology. We could not make enough virus for the kind of impact were having now. But technology has improved, and we can now deliver genes through circulation to reach all muscles.

Regardless of the disease, he said, its extremely important to confirm the patients specific mutation before anything else.

This is critical, because you dont want to deliver the wrong kind of gene in a disease like Friedreichs ataxia. That goes for all gene therapy trials, he said. Next, we want to check for pre-existing antibodies, whether theyre acquired from the environment or from close contact. They bind to the AAV and block entry to the target organ.

Checking for those antibodies requires a blood test. It generally takes 4-7 days to return lab results a nailbiting time for patients and families, Mendell said, because theyre waiting to be approved for enrollment in the trial.

Byrne estimated that 50-60% of all individuals may have been exposed to AAV.

Prior exposure at any level to any AAV infection is an exclusion in most studies, he said, noting that people who travel frequently or who have respiratory or gastrointestinal conditions are particularly susceptible. We are learning a lot about what thresholds are effective. Its about 10% of newborns and about 50% of those of school age and adulthood.

Patients must also be in general good health except, of course, for the genetic disease being treated. MRI and blood tests are done to rule out diabetes or any evidence of heart, liver, or kidney problems.

We put the patient to sleep so theres really no pain involved, Mendell said. We also use local numbing medicine, even though the patient is asleep, so theres no pain or discomfort.

The Powell Gene Therapy Center was established in 1996 the year before Byrne joined UF by Nicholas Muzyczka, PhD, who performed groundbreaking work on AAVs in the 1980s. The center has a dozen individual labs working in neuroscience and molecular genetics.

Byrne said that because gene therapy fundamentally changes many of the bodys cells, screening is crucial.

This is often a one-way street, in that since the effects are long-lasting, other experimental studies may not accept patients who have received gene therapy of any kind in the past, Byrne said. One must have the clinical features required of the study and meet certain functional and age criteria.

To prepare for screening, patients or their parents must read the informed consent and understand what the risks and benefits are. Genetic counseling also may be required to determine whether a given mutation is amenable to gene therapy.

Baseline evaluations are done when its a muscular skeletal disease timed function tests as well as lab tests and a study schedule is established, he said. In many of our studies, we see the patients very frequently, almost every day for the first two weeks. They stay in the area for up to a month. Because were often dealing with rare populations, that makes it convenient for us to evaluate these patients.

Byrne noted that gene therapy is not necessarily durable for the lifespan of the patient. Because the delivered gene does not integrate into the cells own DNA, it is not passed down to newly formed cells.

Some cells, particularly in the liver and muscle, continue to grow throughout childhood and AAV doesnt integrate, so its progressively less effective unless the cells being targeted, as in SMA, are not dividing, he said. Thats an example where newborn screening is critically important to better outcomes.

Mendell said he generally starts patients on prednisone one day before receiving gene therapy in order to suppress liver inflammation, and keeps them on it for 60 days after.

When were in the room, the first thing that happens is the gene is delivered. You push a button and get started, he said. Obviously it must be the correct gene. Its in there, but you cant see it.

The actual gene is delivered by intravenous (IV) infusion with a pump over a 90-minute period, Mendell said; anything faster than that could potentially cause harmful side effects.

We put IVs in both arms for continuous delivery in case one side gets clogged up. We dont want anything to stop gene delivery, he said. Meanwhile, the patient is constantly monitored for vital signs. We invite the whole family to stay together, and thats reassuring. Theres anxiety about gene therapy, but the potential benefits generally outweigh any risks involved.

Some patients may develop nausea and vomiting in the first one-to-three weeks following treatment. For this reason, blood is taken every two weeks for three months to check for side effects.

Mendell said he knows patients are responding to gene therapy by doing testing. In the case of Duchenne, he uses the North Star Ambulatory Assessment, which includes 17 timed tests such as climbing stairs, rising from a sitting position, and walking or running 100 meters. In addition, neck control is a very good indicator of efficacy among Duchenne boys, he said.

The FDA anticipates that within the next 10 years, it will approve up to 40 gene therapies for rare conditions. Mendell said the benefits of gene therapy for one condition in particular, SMA, are undeniable.

This is an absolutely devastating disease. In type 1 SMA, patients usually dont survive past age 2, and about 50% are gone by age 1, he said. Initially there was concern about giving this to infants, but we told the FDA we needed to test infants in order to save lives.

Continuing results from Mendells pivotal Phase 1 trial (NCT02122952) in 15 type 1 infants and along-term extension study (NCT03421977) have changed the way people view gene therapys potential in general.

After four years, he said, every patient in our trial went from being unable to sit to being able to, and several are able to walk. One patient was treated 28 days after birth, and now four years later, hes off to school. What Barry and I do is very gratifying, and we thank our patients and their families for this opportunity.

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Experts Barry Byrne, Jerry Mendell Lead NORD Webinar on Gene Therapy - Muscular Dystrophy News