StemCell Therapy

Genes carry the information that make you you. So it's fitting that, when sequenced and stored in a computer, your genome takes up gobs of memoryup to 150 gigabytes. Multiply that across all the people who have gotten sequenced, and you're looking at some serious storage issues. If that's not enough, mining those genomes for useful insight means comparing them all to each other, to medical histories, and to the millions of scientific papers about genetics.

Sorting all that out is a perfect task for artificial intelligence. And plenty of AI startups have bent their efforts in that direction. On August 3, sequencing company Veritas Genetics bought one of the most influential: seven-year old Curoverse. Veritas thinks AI will help interpret the genetic risk of certain diseases and scour the ever-growing databases of genomic, medical, and scientific research. In a step forward, the company also hopes to use things like natural language processing and deep learning to help customers query their genetic data on demand.

It's not totally surprising that Veritas bought up Curoverse. Both companies spun out of George Church's prolific Harvard lab. Several years ago, Church started something called the Personal Genomics Project, with the goal of sequencing 100,000 human genomesand linking each one to participants' health information. Veritas' founders helped lead the sequencing partstarting as a prenatal testing service and launching a $1,000 full genome product in 2015while Curoverse worked on academic strategies to store and sort through all the data.

But more broadly, genomics and AI practically call out for one another. As a raw data format, a single person's genome takes up about 150 gigabytes. How!?! OK so, yes, storing a single base pair only takes up around two bits. Multiply that by roughly 3 billionthe total number of base pairs in your 23 chromosome pairsand you wind up with around 750 megabytes. But genetic sequencing isn't perfect. Mirza Cifric, Veritas Genetics cofounder and CEO, says his company reads each part of the genome at least 30 times in order to make sure their results are statistically significant. "And you gotta keep all that data, so you can refer back to it over time," says Cifric.

That's just storage. "Everything after that is going to specific areas and asking questions: Theres a variant at this location, a substitution of this base, a deletion here, or multiple copies of this same gene here, here, and here," says Cifric. Now, interpret all that. Oh, and do it across a thousand, hundred thousand, or million genomes. Querying all those genetic variations is how scientists get leads to find new drugs, or figure out how existing drugs work differently on different people.

But cross-referencing all those genomes is just the beginning. Curoverse, which was focusing on projects to store and sort genomic data, also has its work cut out for it in searching through the 6 millionand countingjargon-filled academic papers detailing gene behavior, including visual information found in charts, graphs, and illustrations.

That's pretty ambitious. Natural language processing is one of the stickiest problems in AI. "Look, I am a computer scientist, I love AI and machine learning, and no amount of coding makes sense to solve this," says Atul Butte, the director of UCSF's Institute of Computational Health Sciences. At his former job at Stanford University, Butte actually tried to do the same thinguse AI to dig through genetics research. He says in the end, it was way cheaper to hire people to read the papers and input the findings into his database manually.

But hey, never say never, right? However they accomplish it, Veritas wants to move past what companies like 23andMe and Color offer: genetic risk based on single-variant diseases. Some of America's biggest dangers come from diseases like diabetes and heart disease, which are activated by interactions between multiple genesin addition to environmental factors like diet and exercise. With AI, Cifric believes Veritas will be able to not only dig up these various genetic contributors, but also assign each a statistical score showing how much it contributes to the overall risk.

Again, Butte hates to be a spoilsport, but ... there's all sorts of problems with doing predictive diagnostics with genetic data. He points to a 2013 study that used polygenic testing to predict heart disease using the Framingham Heart Study dataabout as good as you can get, when it comes to health data and heart disease. "They authors showed that yes, given polygenic risk score, and blood levels, and lipid levels, and family history, you can predict within 10 years if someone will develop heart disease," says Butte. "But doctors could do the same thing without using the genome!"

He says the problems come down to just how messy it is trying to square up all the different research on each gene alongside the environmental risks, and all the other compounding factors that come up when you try to peer into the future. "Its been the holy grail for a long time, structured genome reporting," says Butte. Even attempts to get researchers to write and report data in a standard, machine-readable way, have fallen flat. "You get into questions that never go away. One researcher defines autism different from another one, or high blood pressure, or any number of things," he says.

Butte isn't a total naysayer. He says partnerships like the one between Veritas and Curoverse are becoming more commonlike the data processing deal between genetic sequencing giant Illumina and IBM Watsonbecause there's a clear need for new computing methods in this area. "You want to get to a point where you are developing stuff that improves clinical care," he says.

Or how about directly to the owners of the genomes? Cifric hopes the merger will improve the consumer experience of using genetic data, even seamlessly integrating it into daily life. For instance, linking your genome and health records to your digital assistant. Alexa, should I eat this last piece of pizza? Maybe you should skip it, depending on your baseline genetic risk for cholesterol and latest blood test results. Diet isn't the only area where genomics could help improve your day to day life. Some people are more or less sensitive to over the counter drugs. A quick query might tell you whether you should take a little less Tylenol than is recommended.

Cifric thinks this acquisition could position Veritas as a global powerhouse of genomic data. "Apple recently announced that they had shipped 41 million iPhones in a quarter, right? I think in not too distant future, well be doing 41 million genomes in a quarter," he says. That might seem ambitious, given that the cost to consumers is nearly $1,000. But that cost is bound to come down. And artificial intelligence will make paying for the genome a matter of common sense.

This story has been updated to reflect that the company is named Veritas Genetics, not Veritas Genomics.

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Veritas Genetics Scoops Up an AI Company to Sort Out Its DNA - WIRED

DURHAM Millions of people die every year from dehydration as a result of exposure and illness. In humans, even the most minor dehydration can compromise the kidneys causing lifelong, irreparable issues or even death. However, some animals living in desert environments are able to survive both acute and chronic dehydration. While these animals, like cactus mice, have evolved over time to deal with environmental stressors like dehydration, researchers at the University of New Hampshire have found its not the physical makeup that is helping them survive, but rather their genetic makeup.

Initially, we thought that maybe their kidneys are structurally different from people, but theyre not, said Matt MacManes, assistant professor of genome enabled biology at UNH and lead author of the study. However, when exposed to acute dehydration, no kidney injury was apparent, which would definitely be the case for humans exposed to similar levels of dehydration, suggesting their genes may be whats preventing widespread kidney damage.

The kidney is the canary in the coal mine when it comes to dehydration, continues MacManes. The exciting outcome of this research is that the molecular toolkit of the cactus mouse has orthologues, or related genes, in humans. These provide the potential for development of drugs or other therapies that could help protect the human body from the damages of dehydration. Such a response could be extremely valuable in a wide variety of situations for people with renal failure, where water is severally limited due to geography or possibly global climate change, for troops deployed in the desert, and perhaps even in space travel.

To understand how desert-adapted cactus mice (Peromyscus eremicus) survive, the study recently published in the American Journal of Renal Physiology outlines how the researchers modeled a desert-like condition. The mice that went without water for 72 hours lost on average 23 percent of their body weight, which would be fatal for humans. Even though dehydrated, the mice continued to be active, eat, and interact normally. Researchers analyzed several other factors including serum electrolytes (sodium, calcium, bicarbonate ion) as well as blood urea nitrogen (BUN) and creatinine. While both were slightly elevated, gene-based biomarkers for kidney injury, were not, which suggests kidney injury is not occurring.

Further analysis found genes that are important in modulating electrolytes were very active, as were genes responsible for maintaining kidney blood pressure.

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UNH research: Genetics mechanism preventing kidney injury after severe dehydration - Foster's Daily Democrat

It appears, by all accounts, to be a momentous scientific achievement and possibly a turning point in human evolution. In a study released last week, scientists at Oregon Health and Science University confirmed they were able to modify genes in viable human embryos, proving the potential to permanently alter the makeup of a genetic line.

In this case, that meant replacing and repairing a mutated gene that causes a common and deadly heart disorder. But the possibilities heralded by gene-editing technology are endless, the scenarios as divided as they are bold. In some visions, it leads to a population of designer babies or consumer eugenics. Others imagine a utopia of scientific advancement where humans live free of disease, and devastating conditions are eradicated for the betterment of humanity. What direction the technology will take is the topic of much debate.

The big thing which is making the scientific and ethics community get excited, and on the other hand a little bit hot and bothered, is its a mechanism to change genes for multiple generations, says Dr. Alice Virani, a genetic counsellor and director of ethics at British Columbias Provincial Health Services Authority. There are two ways to look at it, the more realistic ramifications and the sci-fi, if-this-was-out-of-control ramifications.

Opinion: Gene editing is not about designer babies

The team at the Oregon universitys Center for Embryonic Cell and Gene Therapy used technology called CRISPR, or Clustered Regularly Interspaced Short Palindromic Repeats, to repair or edit the gene carrying the heart disorder, seemingly with greater success than previous attempts by scientists in China.

News of the research has been anxiously anticipated by many in the field, both for what it means for the potential eradication of a disease such as hypertrophic cardiomyopathy and for the fundamental questions it raises about human reproduction, health and society.

When the study was leaked days before its publication in the journal Nature, its lead scientist, Dr. Shoukhrat Mitalipov, attributed the release to likely a combination of hot words: CRISPR, gene-editing, and designer babies.

The study and its combination of hot words didnt disappoint.

The New York Times hailed the milestone in research, while The New York Post cried BABE NEW WORLD and described an amazing and slightly terrifying breakthrough. A headline on Vox declared simply, This Is Huge.

Even actor Ashton Kutcher tweeted enthusiastically about the scientific breakthrough, writing: Scientists successfully used CRISPR to fix a mutation that causes disease. This is why I wanted to be a geneticist!

The tweet ignited among his followers the same range of responses that are always so keenly tied to the issue of changing human genes, from hope that devastating conditions such as muscular dystrophy will be eradicated, to fear about the unknown consequences of playing God.

Dr. Timothy Caulfield, a Canada Research Chair in Health Law and Policy and professor at the University of Alberta, says the polarized and dramatic response he has seen in recent days reminds him of early reaction to stem-cell science, where, he says, It was either going to be cloned armies, or we were going to eradicate all disease.

In fact, neither has turned out to be the case, and so it may be with gene editing as well.

We need to be cautious not to hype the benefits and be cautious not to hype the ethical concerns, he says. There are real issues on both sides of the debate but lets make sure our discourse is evidence-formed.

He described the new research as a genuinely exciting area, and said the potential of CRISPR which is used not only in human genetics, but also has potentially revolutionary applications for agriculture, animals, plants and food has introduced both exciting possibilities and reasons for deep policy reflection.

Erika Kleiderman, a lawyer and academic whose work focuses on gene-editing technologies, stem-cell research and regenerative medicine at the Centre of Genomics and Policy at McGill University, says the Oregon teams research is exciting because it confirms the ability of CRISPR technology to repair genetic mutations, and establishes the basic safety of the technique in a research context. And while she said people often go straight to thinking about the potential for manipulating genes to create so-called designer babies, a concept that is cool but also quite frightening, the medical implications could be equally staggering, and are far more likely.

For example, something like Huntington disease, she says. Being able to prevent that or treat that one day, in my opinion, would be a fantastic leap for our scientific knowledge and medical advancement. That being said, people will raise the eugenics argument. Is that a possibility? Yes. Are we close to that? I dont think so.

Canada has strict laws around genetic modification and editing, and altering genes in a way that could be passed on to future generations is a criminal offence under the Assisted Human Reproduction Act, punishable with fines up to $500,000 or 10 years in prison.

But as the technology takes a large step forward, Ms. Kleiderman and Dr. Caulfield and are among a group of Canadian scientists and academics calling for less regulation around genetic science and research in Canada, not more.

Both were involved in the creation of an editorial published in the journal Regenerative Medicine in January calling for new consideration of the issues and ethics involved in gene editing, and a revision of Canadian legal policy.

A criminal ban is a suboptimal policy tool for science as it is inflexible, stifles public debate, and hinders responsiveness to the evolving nature of science and societal attitudes, the editorial read. It was signed by seven other experts and ethicists, and came out of a think tank on the future of human gene editing in Canada held at McGill last summer.

Dr. Caulfield says legal prohibition of certain genetic research doesnt make sense when we dont yet know or understand where the science is going, or what the benefits or harms could be. Instead, he says he believes in regulation in problematic areas, while allowing for studies and trials. He says that some of the slippery slope scenarios people fear such as using genetic modification for human enhancement and to achieve superficial traits such as height remain distant possibilities given the complexity of the science.

That is not to say there are not risks or issues to be addressed as the technology continues to evolve. Ms. Kleiderman says that includes consideration of the potential risk to future generations, the safety of the technology and other irrevocable, if unintended, consequences, although she says those risks are not unique to gene modification but true of all technologies.

When it comes to CRISPR, one of the areas it would be most beneficial is with the treatment of prevention of disease which I think most people would be in agreement with, she says. Of course, we need to be mindful of doing not-so-positive things with it, like going down the enhancement route.

She said other potential issues, such as the preservation of human diversity and individuality, the welfare of children born from this technology and the potential for creating new forms of inequality, discrimination or societal conflict, all require significant consideration and research.

There is time. Although the technology is moving quickly, there is still a long way before gene editing is used in clinical human trials. Even after that, Dr. Virani says for the foreseeable future the technology will most likely be used by a small group of people in specific scenarios related to the prevention of serious genetic disease.

Im not saying we shouldnt be concerned about those potential issues, but sometimes we make that leap too quickly, she said. We dont necessarily [think] that the most likely scenario is that couples will use this technology on a very limited basis if they know their child may potentially have a devastating genetic condition. Thats not something that suddenly everyone is going to start to do. I think theres sometimes that leap to, Oh, we can create designer babies, but I think were very much in the lessening-burden-of-disease phase rather than the designer-baby phase, though thats where peoples minds go.

Dr. Virani said one of her own concerns is the possibility of off-target effects, where changing a gene unexpectedly alters something else in the genome. Other concerns are more social reality than science fiction, including that the technology and the ability to prevent disease may only be available to those who can pay for it. Eradicating a horrible disease is one thing. Eradicating it only for families who can afford it is another.

So is it going to look like just the wealthy are going to be able to afford this type of technology? she asks. Thats very problematic in my eyes from an ethics point of view, and thinking about fairness in society. If only poor people get Huntington disease, then the lobby to support Huntington disease research is greatly diminished. Its kind of like a two-fold negative effect.

On Thursday, the American Journal of Human Genetics ran a policy statement signed by 11 organizations from around the world, including the Canadian Association of Genetic Counsellors, urging a cautious but pro-active approach as the science moves forward. The statement includes an agreement that gene editing should not yet be performed in embryos carried on to human pregnancy. (The embryos used in the Oregon research were created only for the research, and were not developed further.) It also outlines a number of criteria that should be met before clinical trials take place, and supports public funding for the research. The U.S. government does not allow federal funding for genetic research on embryos. The Oregon research was funded by the university.

We dont want it to go speeding ahead, said Kelly Ormond, the lead author of the policy statement and a genetics professor at Stanford University in California. We want people to be very transparent about whats happening and we want things to undergo good ethics review, and for society to actually be engaged in these dialogues now while this research is just starting to happen.

She said she believes its important to be pro-active in talking and thinking about the issues related to the technology, and starting a broader conversation of how gene editing should and will be used.

We can all agree that that world [of eugenics and designer babies] doesnt feel very comfortable, and I think most of us dont want to go there, she said. So we need to find ways to prevent that from happening.

Follow Jana G. Pruden on Twitter: @jana_pruden

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Modification of genes in human embryos could mark turning point in human evolution - The Globe and Mail

The global market for stem cells has been estimated at USD 12 billion in 2016and is projected to reach USD 26.6 billion by 2021, at a CAGR of 13.7% during the forecast period 2016to 2021. A stem cell is an undifferentiated cell that has the potential to develop into any type of cell in the body.

Regenerative medicine is the major application of stem cells and other areas are neurology, orthopedics, oncology, cardiology, hematology and others (diabetes, injuries, and wounds). Another prominent application of stem cells is drug discovery and development. The end-users of this market are usually hospitals, cell banks, clinical research laboratories and academic institutes.

Global Stem Cell Marketing Market Dynamics

The global stem cells market is one of the most promising markets in the field of life sciences at present and is forecasted to grow even more in the coming years as stem cells enable cost-effective treatment of many conditions that currently have poor or no treatment.

Drivers

Some of the factors driving the global stem cells market are:

Restraints

While the global stem cells market has ample scope for growth, there are some factors restraining it as well. These include:

The market for stem cells is segmented on the basis of cell types and technology. The cells type segment includes adult stem cells, human embryonic stem cells, induced pluripotent stem cells, rat neural stem cells and very small embryonic-like stem cells. Adult stem cells are again divided into hematopoietic stem cells, mesenchymal stem cells, neuronal stem cells, dental stem cells and umbilical cord cells. The adult stem cells hold the highest share in the global stem cells market, while the market share of induced pluripotent stem cells is expected to grow in the coming years. The technology segment is divided into stem cell acquisition, stem cell production, stem cell cryopreservation, and stem cell expansion sub-segments.

Based on geography, the global market for stem cells is segmented into North America, Europe, Asia-Pacific and Rest of the World. The global stem cells market is dominated byNorth America, followed byEurope, the estimated market share of which is more than 25% as per a recent study. With 30% of the market, the USA holds the majority of share. However, due to increasing awareness among the public and advances in technologies, the market in the Asia-Pacific is expected to grow at a high rate.

Many players in this market are trying to expand their product portfolio in order to top the global market. While some companies are entering into the market by acquisitions, top companies are expanding their growth in this market by acquiring other companies. Few companies have adopted product innovation and new product launches as their key business strategy to ensure their dominance in this market.

Some of the key players in the market are:

Key Deliverables in the Study

If you are in need of BioTechnology marketing or Stem Cell Marketing call 972-800-6670

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BioTech Marketing and market opportunity for Stem Cells - Checkbiotech.org (press release)

Stem cells are the highly versatile spare tires of your body. Once called on, they can replace a damaged cell and, because they aren't yet directed to become part of a specific organ or tissue type, they not only could become (metaphorically speaking) a new tire, but could also fix a worn-out engine part or a cracked windshield. It just takes the right prodding in the body, or the laboratory! They can do it even after being inactive for a long time.

Those remarkable abilities are promising to provide scientists with a powerful tool to use in conquering disease. That's because normally, cells in organs such as the heart and pancreas do not divide to repair damage that might happen to the organ. But manipulation of stem cells ... well, that could allow doctors to induce self-repair in many parts of the body. No more heart transplants; bye, bye diabetes, macular degeneration, spinal cord injury, osteo- and rheumatoid arthritis. We might even repair third-degree burns and stroke damage that was previously considered permanent.

That promising future became more hopeful in 2006, when researchers figured out how to turn specialized adult stem cells (replacing use of embryonic cells in some research) into what they called "induced pluripotent stem cells" (iPSCs). Since then, the number of experiments using iPSCs has sky-rocketed: Adult mouse stem cells are injected into the damaged ventricular wall of a mouse heart and the stem cells regenerated damaged heart muscle! There have been a few, small, human-based studies that, says the National Institutes of Health, have "demonstrated that stem cells that are injected into the circulation or directly into the injured heart tissue appear to improve cardiac function and/or induce the formation of new capillaries." But and this is a big but they caution, "significant technical hurdles remain that will only be overcome through years of intensive research."

Tip: Stem cell clinics promising miracle cures are not a good idea at this time. The International Society for Stem Cell Research says: "Many clinics offering stem cell treatments make claims that are not supported by a current understanding of science."

Fortunately, there's a lot you can do to keep your stem cells healthy and your RealAge younger.

1) Protect your skin from excess sun exposure; use micronized zinc oxide 30 SPF sunscreen. Exposure to ultraviolet radiation from the sun and tanning beds and lamps is a leading cause of melanoma. New research shows that the trigger may be stem cells gone wild; melanoma may be related to the formation of carcinogenic stem cells.

2) Avoid hormone-disrupting chemicals such as BPA in plastics and phthalates in household goods and products. One study found that they disrupt development of stem cells needed for sperm production.

3) Don't overeat; eat whole foods, not chemicals. Steer clear of processed foods that dose you with preservatives, colorings, emulsifiers, added sugars and syrups. Continuous intake of sugary foods reduces stem cell vitality! A lab study found that reducing caloric intake by 20 percent can positively boost stem cell activity. We say, try it five days a month.

4) Get regular exercise. According to a new study out of the University of Rochester, loss of muscle stem cells is the driving force in loss of muscle tone and strength as you age. That makes it increasingly important to get two to three 30-minute sessions of strength-building exercises weekly. Aerobic effort (push it a bit) stimulates some stem cells to produce bone instead of fat.

5) Avoid excess radiation. Exposure to a dental X-ray, PET or CAT scan provides diagnostic benefits without immediate risks. But new evidence shows that accumulative exposure to radiation over a lifetime can have damaging effects on stem cells and organs. Opt for an MRI, not a CAT scan when possible; refuse dental X-rays unless necessary; follow guidelines for mammograms. And make sure your imaging center is accredited, personnel are credentialed, and they use weight-based and indication-based protocols.

Mehmet Oz, M.D. is host of "The Dr. Oz Show," and Mike Roizen, M.D. is Chief Wellness Officer and Chair of Wellness Institute at Cleveland Clinic.

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How to keep your stem cells young - The Garden City Telegram

The advanced technology offered by uBiome may enable us to detect harmful oral bacteria before they endanger the lives of these children - with just a bit saliva.

San Francisco, CA (PRWEB) August 08, 2017

uBiome, the leader in microbial genomics, has issued its latest Microbiome Impact Grant award to pediatric dentist and scientist Dr. Jeremy Horst of UCSF School of Medicine, who, along with colleagues in the UCSF Children's Oral Health Research Center, is carrying out research into the use of the oral microbiome as a non-invasive way of predicting and preventing blood infections in immunocompromised young bone marrow transplant patients.

Bone marrow transplants are used in order to replace damaged or diseased cells with non-cancerous stem cells that can, in turn, grow new, healthy cells. These transplants tend to be used when treatments for cancer have destroyed the bone marrows normal stem cells. Bone marrow, which is found at the core of bones, is where the body manufactures blood cells.

Bone marrow transplants can be either allogeneic or autologous. Allogeneic transplants occur when bone marrow is received from a donor. In autologous transplants, the patients own bone marrow is used, after being collected, frozen, and stored until it is needed following chemotherapy, for example.

Blood infections pose a considerable risk during bone marrow transplants, so being able to predict and prevent them is critical. Dr. Horsts study aims to explore the use of the oral microbiome as a predictive diagnostic for blood infections in pediatric patients who are immunocompromised, a common phenomenon during transplant procedures. Having a weakened immune system, technically known as immunodeficiency, is a state in which the immune systems ability to fight infectious disease and cancer is either compromised or entirely absent.

The potential to use the oral microbiome as a marker for the blood microbiome would offer considerable benefits, particularly because of its non-invasive nature.

Dr. Horst is a Postdoctoral Scholar in the Biochemistry and Biophysics Department at UCSF School of Medicine, specializing in Biochemistry and Infectious Diseases. He received his PhD for studies in Oral and Computational Biology at the University of Washington, after also first gaining his DDS there. This was followed by a residency in Pediatric Dentistry at UCSF. Dr. Horst began his academic studies at UCSD, where he was awarded his BS in Pharmacological Chemistry, a BA in Psychology, and a masters in Chemistry. He has contributed to 40 scientific papers.

The microbiome is the collective term for the ecosystem of trillions of microorganisms that live in and on the human body. Many play important parts in supporting life. For example, gut bacteria aid digestion and enable the synthesis of vitamins. Pathogenic bacteria, however, can be associated with a range of conditions. uBiome employs precision sequencing technology to generate detailed analyses of the human microbiome.

Dr. Jeremy Horst says: To prepare young patients for bone marrow transplant, their immune systems are temporarily wiped out. Despite our extraordinarily cautious efforts, one third of these children at UCSF Benioff Childrens Hospital get blood infections, and oddly enough, one third of the infections come from bacteria in the dental plaque. We use traditional culture-based diagnostics to understand these infections once they happen, but the advanced technology offered by uBiome may enable us to detect harmful oral bacteria before they endanger the lives of these children - with just a bit saliva.

Dr. Zachary Apte, co-founder and CTO of uBiome, adds: After collaborating with him in the past, were familiar with Dr. Horsts work. We think his novel proposal to predict and prevent blood infections in young patients with weakened immune systems using something as simple as a saliva test is very exciting.

Founded in 2012, uBiome is the worlds leading microbial genomics company. uBiome is funded by Y Combinator, Andreessen Horowitz, 8VC, and other leading investors.

uBiomes mission is to explore important research questions about the microbiome and to develop accurate and reliable clinical tests based on the microbiome.

Contact:Julie Taylorjulie(at)ubiome(dot)comPh: +1 (415) 212-9214

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uBiome Grant Will Enable UCSF Scientist to Explore 'Spit Test' to Predict Blood Infections in Young Bone Marrow ... - PR Web (press release)

In 2002, Ian Thompson, a specialist in facial reconstruction at Kings College, London, received an urgent phone call. A patient in his late 20s had been struck by an out-of-control car mounting the pavement. The impact had sent him catapulting over the bonnet of the car, smashing his face and shattering the fragile orbital floor the tiny bone, no more than 1mm thick, which holds the eyeball in place in the skull.

Without the orbital floor, your eye moves backwards into the skull, almost as a defensive mechanism, Thompson explains. But this results in blurred vision and lack of focus. This patient had also lost the ability to perceive colour. His job involved rewiring aircraft and as he could no longer detect a red wire from a blue one, hed barely been able to work in three years.

The accident had happened three years earlier. Since then, surgeons had desperately tried to reconstruct the bony floor and push the eye back into position, first using material implants and then bone from the patients own rib. Both attempts had failed. Each time, infection set in after a few months, causing extreme pain. And now the doctors were out of ideas.

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Thompsons answer was to build the worlds first glass implant, moulded as a plate which slotted in under the patients eye into the collapsed orbital floor. The idea of using glass a naturally brittle material to repair something so delicate may seem counterintuitive.

But this was no ordinary glass.

If you placed a piece of window glass in the human body, it would be sealed off by scar tissue, basically wobble around in the body for a while and then get pushed out, says Julian Jones, an expert in bioglass at Imperial College London. When you put bioglass in the body, it starts to dissolve and releases ions which kind of talk to the immune system and tell the cells what to do. This means the body doesnt recognise it as foreign, and so it bonds to bone and soft tissue, creating a good feel and stimulating the production of new bone.

Bioglass actually works even better than the patients own bone Ian Thompson

For Thompson, the results were immediate. Almost instantaneously, the patient regained full vision, colour and depth perception. Fifteen years on, he remains in full health.

Thompson has gone on to use bioglass plates to successfully treat more than 100 patients involved in car or motorcycle accidents. Bioglass actually works even better than the patients own bone, Thompson says. This is because weve found that it slowly leaches sodium ions as it dissolves, killing off bacteria in the local environment. So, quite by chance, you have this mild antibiotic effect which eliminates infections.

Cutting edge

Bioglass was invented by US scientist Larry Hench in 1969. Hench was inspired by a chance conversation on a bus with an army colonel who recently had returned from the Vietnam War. The colonel told Hench that while modern medical technology could save lives on the battlefield, it could not save limbs. Hench decided to shelve his research into intercontinental ballistic missiles and instead work on designing a bionic material which would not be rejected by the human body.

Hench ultimately took his research to London, and it has been in Britain where some of the most revolutionary bioglass innovations are being made in fields from orthopaedic surgery to dentistry.

Over the last 10 years, surgeons have used bioglass in a powdered form, which looks and feels like a gritty putty, to repair bone defects arising from small fractures. Since 2010, this same bioglass putty has hit the high street as the key component in Sensodynes Repair and Protect toothpaste, the biggest global use of any bioactive material. During the brushing process, the bioglass dissolves and releases calcium phosphate ions which bond to tooth mineral. Over time, they slowly stimulate regrowth.

But many scientists feel that the current applications of bioglass are barely scratching the surface of what could be possible. New clinical products are being developed which could revolutionise bone and joint surgery like never before.

Sitting in his office in Imperial Colleges Department of Materials, Jones is holding a small, cube-shaped object hes dubbed bouncy bioglass. Its similar to the current bioglass but with a slight twist: subtle alterations in the chemical composition mean its no longer brittle. Instead it bounces,like a kids power ball as Jones describes it, and its incredibly flexible.

The point of this is that it can be inserted into a badly broken leg and can support both the patients weight and allow them to walk on it without crutches, without requiring any additional metal pins or implants for support. At the same time, the bouncy bioglass also will stimulate and guide bone regrowth while slowly, naturally assimilating into the body.

To regenerate large pieces of bone, for example in a really big fracture, its very important to be able to put weight on your leg, Jones says. And its really important that the bio-implant in your leg is able to transmit the force from your weight to the bone cells, like a signal. Our body makes its own bone in the architecture that its in, because the cells feel the mechanical environment. So to grow back a big piece of bone you need to be able to transmit the right signals to them. The reason why astronauts in space lose bone mass is because without gravity, the cells arent receiving the same information as they do on Earth.

Further alterations to the chemical makeup of bioglass produce a different form which is much softer and has an almost rubbery feel. It feels almost like a piece of squid at a seafood restaurant. This bioglass is designed for possibly the holy grail of orthopaedic surgery: cartilage repair.

Right now, surgeons attempt to repair damaged cartilage in arthritic hips or damaged knee joints with a fiddly procedure called microfracture. This involves smoothing over the damaged area to expose the bone underneath, then pricking it to release stem cells from the bone marrow which stimulate repair. But this results in scar cartilage and within a few years, as many athletes have found, the original problem returns.

As a solution, Jones is looking to produce bioglass which can be 3D-printed and then slotted into any hole in the cartilage. For the cells to accept it, the material must retain all the natural properties of cartilage. To test its effectiveness, Jones uses a simulator that has human knee joints from cadavers donated for medical research.

We simulate the walking action, bending, all the things a knee would do, and make sure that the bioglass actually preserves the rest of the joint and behaves as it should do, he says. If that works then well proceed to animal and then clinical trials.

This same bioglass could find an additional use in aiding people with chronic back pain due to herniated discs. At the moment surgeons treat this by replacing the dysfunctional disc with a bone graft which fuses the vertebrae in the back together. But while this takes away the pain, it results in a considerable loss in mobility. Instead, a bioglass implant could be printed and simply inserted to replace the faulty disc.

It seems the obvious thing to do, Jones says. So far nobody has been able to replicate the mechanical properties of cartilage synthetically. But with bioglass, we think we can do it.

Weve just got to prove that we can. If all goes well and we pass all the necessary safety tests, it could reach the clinic in 10 years.

Using man-made materials which can fuse to the body may seem far-fetched but it is appearing to be a more and more likely component of future medicine. Already, millions of people brush their teeth with it. And that may just be the start.

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The best way to fix broken bones might be with glass - BBC News

For cancer patients, understanding the odds of a treatments success can be bewildering. The same drug, applied to the same type of cancer, might be fully successful on one persons tumour and do nothing for another one. Physicians are often unable to explain why.

Now, U of T Engineering researchers are beginning to understand one of the reasons.Abdullah Syed and Shrey Sindhwani, both PhD candidates,and their colleagues at the Institute of Biomaterials & Biomedical Engineering (IBBME) have created a technology to watch nanoparticles traveling into tumours revealing barriers that prevent their delivery to targets and the variability between cancers.

The biggest thing weve noticed is that nanoparticles face multiple challenges posed by the tumour itself on their way to cancer cells, says Sindhwani, an MD-PhD student in the Integrated Nanotechnology & Biomedical Sciences Laboratory of Professor Warren Chan (IBBME). Syed and Sindhwani co-published their findings online June 22, and on the cover of the Journal of the American Chemical Society. So the treatment might work for a while or worse, theres just enough of the drug for the cancer to develop resistance. This could be prevented if we can figure out the ways in which these barriers stop delivery and distribution of the drug throughout the cancer.

Tiny nanoparticles offer great hope for the treatment of cancer and other disease because of their potential to deliver drugs to targeted areas in the body, allowing more precise treatments with fewer side effects. But so far the technology hasnt lived up to its promise, due to delivery and penetration problems.

To dismantle this roadblock, the two graduate students searched for a way to better view the particles journey inside tumours. They discovered that the tough-to-see particles could be illuminated by scattering light off their surfaces.

The sensitivity of our imaging is about 1.4 millionfold higher, says Syed. First, we make the tissue transparent, then we use the signal coming from the particles to locate them. We shine a light on the particles and it scatters the light. We capture this scattering light to learn the precise location of the nanoparticles.

It was already understood that nanoparticles were failing to accumulate in tumours, thanks to a meta-analysis of the field done by Chans group. But the researchers have developed technologies to look at nanoparticle distribution in 3D, which provides a much fuller picture of how the particles are interacting with the rest of the tumour biology. The goal is to use this technology to gather knowledge for developing mathematical principles of nanoparticle distribution in cancer, similar to the way principles exist for understanding the function of the heart, says Syed.

And because each tumour is unique, this technology and knowledge base should help future scientists to understand the barriers to drug delivery on a personalized basis, and to develop custom treatments.

The next step is to understand what in cancers biology stops particles from fully penetrating tumours and then to develop ways to bypass cancers defences.

But the technology is also useful for diseases other than cancer. With the help of Professor Jennifer Gommerman, an researcher in the Department of Immunology who studies multiple sclerosis (MS), Syed and Sindhwani captured 3D images of lesions in a mouse model mimicking MS using nanoparticles.

This is going to be very valuable to anyone trying to understand disease or the organ system more deeply, says Sindhwani. And once we understand barriers that dont allow drugs to reach their disease site, we can start knocking them down and improving patient health adds Syed.

More here:
Targeting tumours: IBBME researchers investigate biological barriers to nanomedicine delivery - U of T Engineering News

Empas multicellular model, which is mimicking the placental barrier: a core of connective tissue cells, surrounded by trophoblast cells. Credit: Empa

An Empa team has succeeded in developing a new three-dimensional cell model of the human placental barrier. The "model organ" can quickly and reliably deliver new information on the intake of substances, such as nano-particles, by the placental barrier and on any possible toxic effects for the unborn child. This knowledge can also be used in the future for the development of new approaches to therapy during pregnancy.

During its development, the foetus is extremely susceptible to toxic substances. Even the tiniest doses can cause serious damage. In order to protect the unborn child,one of the tasks of the placenta is to act as a barrier to "filter out" harmful substances, while at the same time providing the foetus with the nutrients it needs. In recent years, however, evidence has increasingly suggested that the placental barrier is not 100 percent effective and that nano-particles are actually able to penetrate it.

Nano-particles are being used in ever more varied areas of our lives. They are used, for example, in sun creams to protect against sunburn; they are used in condiments to stop them getting lumpy; they are used to make outdoor clothing waterproof and they are likely to be used in the future to transport medicines to their rightful destinations in the body . "At the moment, pregnant women are not being exposed to problematic amounts of nano-particles, but in the future that could well happen due to the ever increasing use of these tiny particles," suggests Tina Buerki of the "Department of Particles-Biology Interactions."

In order to ensure the safe development of nano-particles in the most diverse areas of application, their absorption mechanism at the placental barrier and their effect on the mother, foetus and placenta itself must be looked at more closely. It is the size, charge, chemical composition and shape of the nano-particles that could have an influence on whether they actually penetrate the placental barrier and, if so, in what way they are able to do so. At the moment, however, this research is only in its infancy. Since the function and structure of the human placenta is unique, studies undertaken on pregnant mammals are problematic and often inconclusive. Traditional models of the human placental barrier are either very time consuming to construct, or are extremely simplified.

A 3-D model of the human placental barrier

Tests of this nature are best carried out on donated placentas that become available after childbirth by Caesarean section. The organs are connected as quickly as possible to a perfusion system and this ensures the tissue is provided with nutrients and oxygen. This model is, indeed, the most accurate, i.e. the most clinically relevant. It is, however, very technically demanding and, moreover,restricted to a perfusion time window of six to eight hours. Against that, such placentas can be used to reliably test the ability of any given nano-particle to penetrate the placental barrier. The model does not, however, yield any information on the mechanism used by the particle to penetrate this complex organ.

Researchers are therefore tending to fall back on the use of simple cell cultures and other modelling systems. An individual cell, possibly taken from the epithelium and subsequently cultivated and propagated in a petri dish, is perfectly suited to a whole range of different experiments. However, researchers cannot be certain that the cells in the petri dish will ultimately behave like those in the human body. The new model that the Empa team under Tina Buerki described in the scientific journal Nanoscale at the end of last year is, by contrast, three-dimensional and consists of more than one cell type. The cells exist in a tissue-like environment analogous to the placenta and can be experimented on for a longer period of time.

Golden test candidate

In order to create the model, the research team used the "hanging drop" technology developed by Insphero AG. This technology allows models to be created without "scaffolding," which can hinder free access of the nano-particles to the cells in the subsequent transport tests. Rather than introducing the cells in a flat petri dish, a special device, in which the cells in the hanging drops combine to form spherical micro-tissue, is used. The resulting micro-tissue mimics the human placenta much more closely than cells cultivated on a "rigid" culture dish. Experiments can be carried out much more quickly using the 3-D model than with the real placenta and, significantly, on the most widely differing types of nano-particle. In this way, those nano-particles that show potentially toxic effects or demonstrate desirable transport behaviour can be efficiently pre-selected and the results verified using a real placenta.

The model has already proved itself in a second study, which the team has just published in the scientific journal Nanomedicine. Buerki's team has come up with an absorption mechanism for gold particles that could be used in a range of medicinal applications. The Empa team looked at gold particles of various sizes and different surface modifications. In accordance with the results of other studies, the researchers discovered that small gold particles were able to penetrate the placental barrier more easily. In addition, fewer particles passed through the barrier if they were carrying polyethylene glycol (PEG) on their surfaces. These are chain-forming molecules that almost completely envelope the particles. PEG is often used in medicine to allow particles and other small structures to travel "incognito" in the body, thus preventing them being identified and removed by the immune system. "It therefore appears possible to control the movement of nano-particles through the placenta by means of their properties," Buerki explains.

Medicines for pregnant women that do not harm the child

Empa's research team is keen to further develop this 3-D model in the future. The team is hoping to augment the model using a dynamic component. This would, for example, mean introducing the micro-tissue in a micro-fluid system able to simulate blood circulation in the mother and child. Another approach would be to combine the model of the placenta with other models. "With the model of a foetus, for example," Buerki suggests. In this way, complex organ interactions could also be incorporated and it would be possible, for example, to discover whether the placenta releases foetus-damaging substances as a reaction to certain nano-particles.

"With these studies, we are hoping to lay the foundations for the safe but nevertheless effective use of nano-medicines during pregnancy," Buerki continued. If we understand the transport mechanisms of nano-materials through the placental barrier well enough, we believe we can develop new carrier systems for therapeutic agents that can be safely given to pregnant women. This is because many women are forced to take medicines even during pregnancy patients suffering from epilepsy or diabetes, for example, or patients that have contracted life-threatening infections. Nano-carriers must be chosen which are unable to penetrate the placental barrier. It is also possible, for example, to provide such carriers with "address labels," which ensure that the medicine shuttle is transported to the correct organ i.e. to the diseased organ and is unable to penetrate the placenta. This would allow the medicine to be released first and foremost into the mother. Consequently, the amounts absorbed by the foetus or embryoand therefore the risk to the unborn child are significantly reduced.

Explore further: New placenta model could reveal how birth defect-causing infections cross from mom to baby

Continued here:
Medication for the unborn baby - Medical Xpress

By Ben Hirschler

LONDON (Reuters) - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

Glybera, costing around $1 million per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win U.S. approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get a U.S. go-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centers in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400 million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1 million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

"In an area like haemophilia I think that approach is going to make a ton of sense, since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where specialty drugmakers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1 billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Read more from the original source:
Gene Therapy Is Now Available, but Who Will Pay for It? - Scientific American

LONDON (Reuters) - Gene therapy, which aims to patch faulty genes with working DNA, has been a long time in development. The following are major milestones:

1972 - Researchers first suggest gene therapy as a treatment for genetic diseases but oppose its use in humans "for the foreseeable future", pending greater understanding of the technology.

1990 - A four-year-old girl with severe immunodeficiency became the first patient to undergo gene therapy in the United States.

1999 - American patient Jesse Gelsinger dies following a gene therapy experiment, setting the field back several years as U.S. regulators put some experiments on hold.

2002-03 - Cases of leukaemia are diagnosed in French children undergoing gene therapy in a further blow to the field.

2003 - The world's first gene therapy is approved in China for the treatment of head and neck cancer.

2007 - Doctors carry out the world's first operation using gene therapy to treat a serious sight disorder caused by a genetic defect.

2012 - Europe approves Glybera, the first gene therapy in a Western market, for an ultra-rare blood disorder.

2016 - Europe approves Strimvelis for a very rare type of immunodeficiency.

2017 or 2018 - The first gene therapy could be approved in United States.

Reporting by Ben Hirschler; editing by David Stamp

Read more from the original source:
Timeline: Gene therapy's long road to market - Reuters

LONDON - The science of gene therapy is finally delivering on its potential, and drugmakers are now hoping to produce commercially viable medicines after tiny sales for the first two such treatments in Europe.

Thanks to advances in delivering genes to targeted cells, more treatments based on fixing faulty DNA in patients are coming soon, including the first ones in the United States.

Yet the lack of sales for the two drugs already launched to treat ultra-rare diseases in Europe highlights the hurdles ahead for drugmakers in marketing new, extremely expensive products for genetic diseases.

After decades of frustrations, firms believe there are now major opportunities for gene therapy in treating inherited conditions such as haemophilia. They argue that therapies offering one-off cures for intractable diseases will save health providers large sums in the long term over conventional treatments which each patient may need for years.

In the past five years, European regulators have approved two gene therapies - the first of their kind in the world, outside China - but only three patients have so far been treated commercially.

UniQure's Glybera, for a very rare blood disorder, is now being taken off the market given the lack of demand.

The future of GlaxoSmithKline's Strimvelis for ADA-SCID - or "bubble boy" disease, where sufferers are highly vulnerable to infections - is uncertain after the company decided to review and possibly sell its rare diseases unit.

READ:Researchers use gene editing on human embryo for first time in US

Glybera, costing around $1-million (R13-million) per patient, has been used just once since approval in 2012. Strimvelis, at about $700,000, has seen two sales since its approval in May 2016, with two more patients due to be treated later this year.

"It's disappointing that so few patients have received gene therapy in Europe," said KPMG chief medical adviser Hilary Thomas. "It shows the business challenges and the problems faced by publicly-funded healthcare systems in dealing with a very expensive one-off treatment."

These first two therapies are for exceptionally rare conditions - GSK estimates there are only 15 new cases of ADA-SCID in Europe each year - but both drugs are expected to pave the way for bigger products.

The idea of using engineered viruses to deliver healthy genes has fuelled experiments since the 1990s. Progress was derailed by a patient death and cancer cases, but now scientists have learnt how to make viral delivery safer and more efficient.

Spark Therapeutics hopes to win US approval in January 2018 for a gene therapy to cure a rare inherited form of blindness, while Novartis could get the USgo-ahead as early as next month for its gene-modified cell therapy against leukaemia - a variation on standard gene therapy.

At the same time, academic research is advancing by leaps and bounds, with last week's successful use of CRISPR-Cas9 gene editing to correct a defect in a human embryo pointing to more innovative therapies down the line.

Pay-for-performance

Spark Chief Executive Jeffrey Marrazzo thinks there are specific reasons why Europe's first gene therapies have sold poorly, reflecting complex reimbursement systems, Glybera's patchy clinical trials record and the fact Strimvelis is given at only one clinic in Italy.

He expects Spark will do better. It plans to have treatment centres in each country to address a type of blindness affecting about 6,000 people around the world.

Marrazzo admits, however, there are many questions about how his firm should be rewarded for the $400-million it has spent developing the drug, given that healthcare systems are geared to paying for drugs monthly rather than facing a huge upfront bill.

A one-time cure, even at $1-million, could still save money over the long term by reducing the need for expensive care, in much the same way that a kidney transplant can save hundreds of thousands of dollars in dialysis costs.

But gene therapy companies - which also include Bluebird Bio, BioMarin, Sangamo and GenSight - may need new business models.

One option would be a pay-for-performance system, where governments or insurers would make payments to companies that could be halted if the drug stopped working.

READ:20 years after cloning Dolly: Everything you always wanted to know

"In an area like haemophilia I think that approach is going to make a tonne of sense since the budget impact there starts to get more significant," Marrazzo said.

Haemophilia, a hereditary condition affecting more than 100,000 people in markets where speciality drug makers typically operate, promises to be the first really big commercial opportunity. It offers to free patients from regular infusions of blood-clotting factors that can cost up to $400,000 a year.

Significantly, despite its move away from ultra-rare diseases, GSK is still looking to use its gene therapy platform to develop treatments for more common diseases, including cancer and beta-thalassaemia, another inherited blood disorder.

Rivals such as Pfizer and Sanofi are also investing, and overall financing for gene and gene-modified cell therapies reached $1-billion in the first quarter of 2017, according to the Alliance of Regenerative Medicine.

Shire CEO Flemming Ornskov - who has a large conventional haemophilia business and is also chasing Biomarin and Spark in hunting a cure for the bleeding disorder - sees both the opportunities and the difficulties of gene therapy.

"Is it something that I think will take market share mid- to long-term if the data continues to be encouraging? Yes. But I think everybody will have to figure out a business model."

Reuters

See original here:
Drugmakers' hopes for gene therapy rise despite tiny sales in Europe - eNCA

Updated Aug. 8, 2017 at 7:02 a.m.

Published: 2017-08-07 16:07:00 Updated: 2017-08-08 07:02:05

Sanford, N.C. Pharmaceutical giant Pfizer Inc. plans to invest $100 million in its Sanford operations as part of a push into gene therapy, officials said Monday.

The effort builds on a technology developed at the University of North Carolina at Chapel Hill and will create 40 jobs in Sanford.

"Pfizer is proud to further expand our presence in North Carolina, particularly as we build our leadership in gene therapy," Lynn Bottone, site leader at Pfizer Sanford, said in a statement. "We look forward to the next phase of this expansion as we build a clinical and commercial manufacturing facility."

Preliminary work on the expansion and initial hiring have already begun. The 230-acre campus employs about 450 people, reports the N.C. Biotechnology Center.

Gene therapy is a potentially transformational technology for patients that involves highly specialized, one-time treatments to address the root cause of diseases caused by genetic mutation. The technology involves introducing genetic material into the body to deliver a correct copy of a gene to a patients cells to compensate for a defective or missing gene.

Last year, Pfizer acquired Bamboo Therapeutics Inc., a privately held biotechnology company in Chapel Hill focused on developing gene therapies for the potential treatment of patients with certain rare diseases related to neuromuscular conditions and those affecting the central nervous system. Pfizer also committed $4 million to support postdoctoral fellowships in North Carolina universities for training in gene therapy research.

"We are excited that Carolinas research will improve lives and create jobs for North Carolinians," UNC-Chapel Hill Chancellor Carol Folt said in a statement. "This is a perfect example of how placing innovation at the center of our university creates new opportunities. We are proud to be a part of the technologies, expertise and infrastructure that went into Bamboo Therapeutics and helped make this manufacturing expansion in Sanford possible. Gene therapy is a strength at Carolina, and we look forward to continue to help advance this industry."

Pfizer is also expanding a drug-manufacturing facility in Rocky Mount that it acquired from Hospira in 2015. The $190 million project will add 65,000 square feet of sterile injectable facilities but will not create any new jobs. The plant employs about 300 people.

Gov. Roy Cooper visited Pfizers Sanford facility last week to take a tour and meet with the companys senior leaders.

"North Carolina is one of the few places in the country with the biotech resources to take an idea all the way from the lab to the manufacturing line," Cooper said in a statement. "Pfizers investment in Lee County is a prime example of how North Carolinas world-class universities and cutting-edge industries work together to move our state forward."

Pfizer qualified for a performance-based grant of $250,000 from the One North Carolina Fund, which provides state assistance matched by local governments to help attract economic investment and create jobs. Companies receive no money upfront and must meet job and investment targets to obtain payment.

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Pfizer to invest $100M in Sanford gene therapy operation, add jobs ... - WRAL Tech Wire

Bluebird Bio plans to bring its gene therapies to market in Europe before the U.S., thanks to a favorable regulatory pathway.

Bluebird's head of Europe, Andrew Obenshain, told the Daily Telegraph that the company is already in negotiations with the EMA and the U.K.'s Medicine and Healthcare products Regulatory Agency (MHRA) on possible regulatory filings.

The EMA's adaptive pathways processwhich allows new therapies to be approved in stages based on stepwise collection of datais a key part of that decision, as is the fact that the agency "works very closely with companies coming forward with new methodologies," said Morgan. And with Brexit looming, it makes sense to discuss these plans with the MHRA separately.

Two years ago, Bluebirdwhich targets severe genetic diseases and cancerwas hit hard when the NorthStar trial of lead therapy LentiGlobin failed to hit the mark in sickle cell disease and beta thalassemia, mainly because of variable patient responses to the treatment.

In a recent SEC filing, the company said that combined data from Northstar and other trials, including a follow-up Northstar-2 study, "could support the filing of a marketing authorization application in the EU" for transfusion-dependent thalassemiaprovided they all meet the primary objective of freeing patients from the need for regular blood transfusions.

So far, no approved gene therapies have been in the U.S., while Europe has seen two approvals, namely for UniGene's Glybera (alipogene tiparvovec) for lipoprotein lipase deficiency and GlaxoSmithKline's Strimvelis for the ultrarare "bubble boy syndrome," or ADA-SCID.

Even getting approval is no guarantee of success, however. Glybera was taken off the market in April due to a lack of demand for the 1 million (around $1.2 million)-per-year therapy, with only one patient receiving it commercially since its launch in 2012.

GSK, meanwhile, has priced Strimvelis at a lower rate (around $650,000 a year) to try to encourage takeup, but hasn't given any updates and said last week it may put its rare disease unit up for sale. Rare disease head Carlo Russo moved to Italian biotech Genenta in January.

More here:
Bluebird Bio sees Europe as first market for its gene therapies - FierceBiotech

A University of Chicago-based research team has overcome challenges that have limited gene therapy and demonstrated how their novel approach with skin transplantation could enable a wide range of gene-based therapies to treat many human diseases.

In a study inthe journal Cell Stem Cell, the researchers provide proof-of-concept. They describe gene-therapy administered through skin transplants to treat two related and extremely common human ailments: Type 2 diabetes and obesity.

We resolved some technical hurdles and designed a mouse-to-mouse skin transplantation model in animals with intact immune systems, said study author Xiaoyang Wu, assistant professor in the Ben May Department for Cancer Research at the University of Chicago. We think this platform has the potential to lead to safe and durable gene therapy in mice and, we hope, in humans, using selected and modified cells from skin.

Beginning in the 1970s, physicians learned how to harvest skin stem cells from a patient with extensive burn wounds, grow them in the laboratory, then apply the lab-grown tissue to close and protect a patients wounds. This approach is now standard. However, the application of skin transplants is better developed in humans than in mice.

The mouse system is less mature, Wu said. It took us a few years to optimize our 3-D skin organoid culture system.

This study is the first to show that an engineered skin graft can survive long term in wild-type mice with intact immune systems. We have a better than 80 percent success rate with skin transplantation, Wu said. This is exciting for us.

The researchers focused on diabetes because it is a common non-skin disease that can be treated by the strategic delivery of specific proteins.

They inserted the gene for glucagon-like peptide 1 (GLP1), a hormone that stimulates the pancreas to secrete insulin. This extra insulin removes excessive glucose from the bloodstream, preventing the complications of diabetes. GLP1 can also delay gastric emptying and reduce appetite.

Using CRISPR, a tool for precise genetic engineering, they modified the GLP1 gene. They inserted one mutation, designed to extend the hormones half-life in the blood stream, and fused the modified gene to an antibody fragment so that it would circulate in the blood stream longer. They also attached an inducible promoter, which enabled them to turn on the gene to make more GLP1, as needed, by exposing it to the antibiotic doxycycline. Then they inserted the gene into skin cells and grew those cells in culture.

When these cultured cells were exposed to an air/liquid interface in the laboratory, they stratified, generating what the authors referred to as a multi-layered, skin-like organoid. Next, they grafted this lab-grown gene-altered skin onto mice with intact immune systems. There was no significant rejection of the transplanted skin grafts.

When the mice ate food containing minute amounts of doxycycline, they released dose-dependent levels of GLP1 into the blood. This promptly increased blood-insulin levels and reduced blood-glucose levels.

When the researchers fed normal or gene-altered mice a high-fat diet, both groups rapidly gained weight. They became obese. When normal and gene-altered mice got the high-fat diet along with varying levels of doxycycline, to induce GLP1 release, the normal mice grew fat and mice expressing GLP1 showed less weight gain.

Expression of GLP1 also lowered glucose levels and reduced insulin resistance.

Together, our data strongly suggest that cutaneous gene therapy with inducible expression of GLP1 can be used for the treatment and prevention of diet-induced obesity and pathologies, the authors wrote.

When they transplanted gene-altered human cells to mice with a limited immune system, they saw the same effect. These results, the authors wrote, suggest that cutaneous gene therapy for GLP1 secretion could be practical and clinically relevant.

This approach, combining precise genome editing in vitro with effective application of engineered cells in vivo, could provide significant benefits for the treatment of many human diseases, the authors note.

We think this can provide a long-term safe option for the treatment of many diseases, Wu said. It could be used to deliver therapeutic proteins, replacing missing proteins for people with a genetic defect, such as hemophilia. Or it could function as a metabolic sink, removing various toxins.

Skin progenitor cells have several unique advantages that are a perfect fit for gene therapy. Human skin is the largest and most accessible organ in the body. It is easy to monitor. Transplanted skin can be quickly removed if necessary. Skins cells rapidly proliferate in culture and can be easily transplanted. The procedure is safe, minimally invasive and inexpensive.

There is also a need. More than 100 million U.S. adults have either diabetes (30.3 million) or prediabetes (84.1 million), according the Centers for Disease Control and Prevention. More than two out of three adults are overweight. More than one out of three are considered obese.

Additional authors of the study were Japing Yue, Queen Gou, and Cynthia Li from the University of Chicago and Barton Wicksteed from the University of Illinois at Chicago. The National Institutes of Health, the American Cancer Society and the V Foundation funded the study.

Article originally appeared on Science Life.

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Gene therapy via skin could treat diseases such as obesity - UChicago News

BioMarin Pharmaceutical on Monday dedicated its new Novato manufacturing facility which is expected to be key in its continuing clinical trials on a drug the company believes will potentially genetically repair the cause of hemophilia A.

Before a crowd of 300 to 400 people, the company, which manufactures drugs mostly for rare diseases, called its new production location the largest gene-therapy-manufacturing facility in the world. The project was completed 11 months ahead of schedule, employing 300 people in 200,000 construction hours, according to Robert Baffi, the firms executive vice president, Technical Operations.

Jean-Jacques Bienaim, chairman and CEO of BioMarin, said the drug to be produced at the location, BMN 270 gene therapy for hemophilia A, has the potential to change what future doctors learn about hemophilia.

Because of a genetic flaw, the blood of those who have hemophilia does not clot. The mutation takes places in a single gene that provides instructions to make a protein called Factor VIII, which is essential for blood to clot normally.

According to the company, the drug thus far in investigational clinical trials has shown the ability to genetically correct the problem and allow patients to manufacture and maintain a constant level of Factor VIII. Production of the drug to be used in those continuing trials will begin as soon as possible in Novato.

Among those affected by the hemophilia is the son of Christine Orr a speaker at todays event. Genetic roulette resulted in an older son being born without the problem.

But soon after her younger son was born, it became apparent he had little or no clotting factor. Every other day, home infusions of clotting factor have helped curb the problem, but she said her son experienced the stigma of parents being afraid to invite him to birthday parties or play dates over what might happen if he were to be hurt.

She said a one-shot treatment to potentially genetically treat and cure the disease gives her hope that yes, a cure is on my horizon, and he can choose his path in life and not have hemophilia choose it for him.

On Aug. 2, BioMarin Pharmaceutical reported it reaped $317 million in second-quarter revenue, up 6 percent from the same quarter in 2016.

It operated a loss of $37 million for the second quarter, but far less than the $419 million loss in the same quarter last year. The last quarters losses amounted to 21 cents per diluted share.

BioMarin, which has six main drugs on the market, had two huge contributors to second-quarter revenue: Kuvan, with $102 million, and Vimizim, with $103 million.

Kuvan, sapropterin dihydrochloride, treats a genetic disorder called phenylketonuria. BioMarin bought global rights to Kuvan in 2015 from Merck for 340 million euros, about $405 million. PKU is rare, and causes amino acid phenylalanine to build up in the body. The buildup of the amino acid can cause grave health problems.

Vimizim treats patients with mucopolysaccharidosis type IV-A, also called Morquio A syndrome, which is a metabolic disorder that inhibits the bodys ability to process certain mucopolysaccharides. It is usually inherited.

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BioMarin Pharmaceutical launches gene therapy drug plant in Novato - North Bay Business Journal

SAN DIEGO, Aug. 8, 2017 /PRNewswire/ --AVACEN Medical (AVACEN) announced partnering with Morulaa HealthTech of Chennai, India to introduce its FDA-cleared AVACEN 100, Class II medical device, in India for treating the joint pain associated with Arthritis which is currently being used in the USA.

According to the World Health Organization, Arthritis affects approximately 200 million people in India. This prevalence is higher than many well-known diseases such as diabetes and cancer. This has a devastating impact on those who suffer from the arthritis and their personal support systems. In addition, arthritis imposes a large economic burden on public and private healthcare providers.

AVACEN recently received CE (Conformit Europenne) Mark approval to market the AVACEN 100 to the European Union's 28 member countries for treating the joint pain associated with Arthritis. AVACEN believes this is the first time a medical device has been approved for treating whole-body arthritis pain.

Currently used in the USA the AVACEN 100 uses an entirely new concept to treat Arthritis pain. It noninvasively and safely infuses heat into the circulatory system forcing the body to dilate peripheral capillaries to radiate off this excess heat.

AVACEN Medical CEO Thomas Muehlbauer described the AVACEN 100 as "the only medical device on the market today able to provide non-invasive, whole-body treatment, using a single point of contact. It is the ideal drug-free and safe alternative for rapid relief of arthritis pain from the inside". Muehlbauer added, "With approximately 2 million safe treatments, we frequently hear reports dramatic results such as being able to return to playing piano, gardening, and chopping vegetables. Even gnarled hand joints have been reported to disappear."

About AVACEN 100 Patents

The US Patent Office has issued 4 Patents to AVACEN which include apparatus claims directed to features of the Heat Therapy apparatus manufactured by AVACEN and method claims directed to specific methods of use, referred to by the company as the AVACEN Treatment Method. The patents also cover innovations embodied in the AVACEN 100 system, which is expected to allow multiple therapeutic uses to alleviate symptoms associated with a circulatory, neurological, lymphatic, or endocrinal dysfunction, or any combination thereof.

Patents have also been issued for China, Australia, Japan, UK, France, Germany, Spain, Sweden and Canada. Patents are pending in India and Hong Kong.

AboutAVACEN Medical

AVACEN Medical is dedicated to the innovation and design of safe, easy to use, noninvasive drug-free alternatives for wound-healing and the management of pain associated with numerous chronic and acute conditions including the temporary relief of minor muscle and joint pain and stiffness associated with arthritis and potentially other conditions that can cause joint pain, such as CRPS, Reynaud's, and Lyme Disease. Founded in 2009, AVACEN Medical is headquartered in San Diego. Contact: Ryan Jeffcoat at (888) 428-2236 x 711 or info@AVACEN.com.

About Morulaa HealthTech

Established by a family with over 100 years of experience in business, Morulaa HealthTech provides turnkey solutions for manufacturers and distributors in the Medical Device sectors. The unique Morulaa model for Product Registration and Distribution, uses in-house regulatory and marketing teams working in-sync with clients to commercialize healthcare products across India and South East Asia. Morulaa HealthTech currently has clients from America, Europe, Asia and Oceania. For more information: http://www.morulaa.com

IMPORTANT NOTES: The AVACEN 100 is not for sale in the U.S. or E.U. for any non-cleared or non-approved indication mentioned in this document.

E.U. CE-Approval: A heat therapy system indicated for the temporary relief of minormuscle and joint pain and stiffness; the temporary relief of joint pain associated witharthritis, muscle spasms, minor strains and sprains;the temporary relief of widespreadpain associated with fibromyalgia; muscular relaxation; andthe temporary increase ofmicrocirculation.

U.S. FDA-Clearance: A heat therapy system indicated for the temporary relief of minor muscle and joint pain and stiffness; the temporary relief of joint pain associated with arthritis; muscle spasms; minor strains and sprains; muscular relaxation; and the temporary increase of local circulation where applied.

View original content with multimedia:http://www.prnewswire.com/news-releases/avacen-medical-introduces-new-concept-for-treating-arthritis-pain-to-india-300501093.html

SOURCE AVACEN Medical

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AVACEN Medical Introduces New Concept for Treating Arthritis Pain to India - PR Newswire (press release)

Joint pain and stiffness are common complaints doctors hear from patients. Personal health advocate Carrie Bloemers says, arthritis is a common problem that can lead to joint swelling and pain. Its really uncomfortable and its something that people experience and live with daily.

There are natural things patients can do to minimize the pain without taking medication. The foods we eat can increase the inflammation levels in our body so therefore, if we are able to follow an anti-inflammatory diet with antioxidants we can help control some of the symptoms of arthritis and inflammation, said Bloemers.

Antioxidants lower levels of inflammation throughout the body. The goal is to minimize the overall symptoms so the aches and the pains from arthritis so they may have a lower dependency on some of the medications they are taking, said Bloemers.

Foods high in antioxidants like blueberries, grapes, and greens, can help with joint inflammation. But processed foods and foods in high fat and sugar can keep your joints inflamed. Not only do we need our blues and our purples, we need red, yellow, orange, and green nutrients so plant based materials every day too, said Bloemers.

A regular healthy diet can help with day to day pain and swelling. Eating blueberries one time isnt going to make your knee feel better. Its your habits of including a healthy diet high in antioxidants, low in inflammatory foods, like high fatty processed meats or high sugar foods that over time are going to help lower the inflammation in your body, said Bloemers.

In addition to fruits and vegetables, health experts also recommend patients maintain an active lifestyle to prevent joint stiffness.

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Health Matters: Nutrition for Inflammation and Arthritis - NBC2 News

Scientists from IIT Guwahati have synthesised mats made of silk-proteins and bioactive glass fibres that they believe can assist the growth of bone cells and repair worn-out joints in arthritis patients.

The disease most commonly affects joints in the knees, hips, hands, feet, and spine and is marked by the breakdown of joint cartilage and underlying bones. Left untreated, it can cause severe pain, swelling, and eventually limited range of movement.

Current clinical treatment methods are limited by lack of viable tissue substitutes to aid the repair process, Biman B. Mandal from institute said.

Joint disease

To develop a suitable tissue substitute, scientists, including those from the University College London in the U.K., looked into the natural bone-cartilage interface and tried to mimic it synthetically in lab conditions.

Knee osteoarthritis is the most common bone and joint disease in India. However, Mr. Mandal pointed out that the available clinical grafts were expensive.

Enhances healing

We used silk, a natural protein to fabricate electrospun mats to mimic the cartilage portion and bioactive glass to develop a composite material, similar to the natural tissue, said Mr. Mandal.

For the mat, scientists used a kind of silk easily available in northeast India.

Muga [Assam] silk is endowed with properties that enhance the healing process, Mr. Mandal said.

The researchers adopted a green fabrication approach for the developing the silk composite mats electrospinning. It is similar to knitting, except that it utilises electric high-voltage force to draw ultrafine fibres, Mr. Mandal said.

A layer by layer approach was followed, where the bone layer was first formed, on top of which the cartilage layer was developed. The resulting composite mat resembled the architecture of the bone-cartilage interface.

To assist the regenerative process, the mats would be grafted in the defected joint with cells harvested from the patient.

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Silk mats that could treat arthritis - The Hindu

A middle-aged tiger has been put down by vets after the endangered predator suffered for years with ARTHRITIS.

Indah, the 12-year-old Sumatran tiger, was a favourite among visitors to Howletts Wild Animal Park with her tiger boyfriend Amir.

But sadly, she was being treated by vets and a leading orthopaedic surgeon but in recent weeks was suffering increasing pain which could not be controlled and had to be put down.

The average Sumatran tiger lives to the age of 24, meaning poor Indah died in the middle of her life, leaving her mate Amir all alone.

A park spokesman said: Following numerous evaluations and discussions, our animal director, vet team and keepers made the difficult decision to euthanise Indah.

This was the most necessary and humane course of action.

Indah was a very special animal, born in 2005 at Dudley Zoo.

Tigress Indah who has had to be put down at Howletts Wild Animal Park.

She arrived at Howletts Wild Animal Park as part of a breeding programme in 2006.

She had a lovely character and was a favourite with visitors and staff alike.

She had a very special bond with Amir our male Sumatran tiger.

The pair would always enjoy a good head rub in the morning and they enjoyed nothing more than sitting out on the high platform in their enclosure, soaking up the sunshine.

We are sure that our visitors and supporters will be as saddened by this news as we are.

Visitors to the park were quick to pay tribute to Indah.

Ellie Hadlington said: My heart goes out to her keepers, who are no doubt distraught.

I commend the keepers and the vet team for the amazing work they have done with her and the other animals.

Tracy Butler added: I met this beautiful tiger when i had time feeding the tigers and gave her meds in piece of meat, such a beautiful creature and a great loss, well done to Howletts for everything they done for her.

Jackie Smith said: Such sad news. So glad I got to see her a few weeks ago. Such a beautiful tiger. Thoughts are with her keepers.

The Sumatran tiger has been listed as critically endangered since 2008, as the population was estimated at 441 to 679.

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With nobody to hold the rich and powerful to account, or report on the issues that don't fit with the mainstream 'narrative', your help is needed.

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HeartbreakingSumatran tiger had to be put down because she had arthritis - The London Economic