Exercising and eating better as part of our new year health kicks are great, but we should also think more deeply about the role the environment plays on our health. As a professor of environmental medicine, I believe this is an exciting new area of study that will play a big part in the future of personalized medicine.

Consider this, every day we are bombarded with messages: genes that cause cancer, supplements that prevent Alzheimers disease, diets that prevent asthma, chemicals that make us gain weight. But while headlines frequently proclaim game changing new findings, over the last 20 years in the US and Europe our health status as a population has seriously deteriorated. Rates of obesity, diabetes, heart disease, cancer and learning disorders continue to rise. Genetic variation may be part of the puzzle that explains why we get sick, but clearly there are missing pieces.

After all, 20 years of increasing obesity and diabetes represents only a single generation. If our genes didnt change in the last 20 years, then our environment must have.

Genes never work in isolation. Instead, they determine how we react to our diet, social surroundings, physical environment, infections and chemical exposures. Environment is the missing piece of the puzzle.

The old 20th-century concept of nature v nurture needs to be redefined, as genetics and environment do not compete, they work hand in hand, sometimes to our benefit and sometimes to our detriment. The correct formula is really nature times nurture. Right now the nurture part of that equation is largely unknown, but that may soon change.

Recently, a new concept has arisen, the science of the exposome: the measurement of all the health-relevant environmental factors across the lifetime.

The exposome is to our environment what genomics is to our genetics. Most of what we know about environment and health is still a black box consisting of yet to be discovered risk factors we too often attribute to bad luck ie because we dont measure the environmental cause, the problem appears random.

But most of what we now understand about genetics was also a black box in the 20th century.

Physicians see the role of environment daily even if it is not clear to them that environment is the cause. For example, a child with autism develops more frequent combative oppositional behaviors and emotional outbursts. An adult with diabetes cant seem to control her blood sugar despite higher doses of insulin. A newborn is born with blue skin but a normal heart.

For each of these cases, sequencing the genome would not have identified the cause. The autistic child had lead poisoning because of pica brought on by autism, the diabetic adult used perfumes high in phthalates, chemicals that affect metabolism and the newborn baby drank formula mixed with well water contaminated by fertilizer runoff that reacted with his hemoglobin.

In each case, genomics would not have given us the correct answer, but if we had the tools to measure the exposome, we would have made the correct diagnosis. Just as importantly, because the underlying causes were environmental, we can treat the problem with interventions.

Furthermore, in most diseases, environment and genetics work in combination. Its very rare to have a genetic variant that causes Alzheimers disease, but it is fairly common to have a genetic variant that makes us susceptible to environments that can cause Alzheimers. The different between those with the genetic variant who get sick and those who dont is their different environments.

Imagine a visit to your physician in which you begin by handing over your smartwatch to have its data downloaded, followed by a blood draw to measure your chemical environment and nutritional status, then you update your lifetime home address and occupational history into a secure computer that houses your genomic data. This then computes your personalized risk score for heart disease, diabetes and other diseases. Or, if you already have one of these diseases, computes the ideal treatment regimen based on this big data. This is how we will be able to personalize medicine.

We are not there yet, but the technology to measure the exposome is far more advanced than the general public, and even many researchers, realize. There are now lab tests that can demonstrate the presence of thousands of chemicals in our bodies and satellites that record our daily weather, air pollution, light exposure and built environment. Public records have data on water quality, age of housing, local crime statistics, outdoor noise levels and even where disease clusters are occurring. Cellphones are ubiquitous and can link our daily behavior and movement patterns with the quality of the local air and water while simultaneously measuring our heart rate, physical activity and sleep quality.

Computational science has advanced to a point where storage of terabytes of data is routine and computer clusters are found in every major university and methods to bring these databases together are no longer science fiction. Artificial intelligence and other big data approaches to genomics also provide a roadmap for analyzing exposomic data.

Understanding how environment affects your health will empower people to make the changes in their lifestyle that will matter most. To understand what food to buy, which fragrances to avoid, where and when to exercise, etc. All the pieces to solve this puzzle are beginning to come together. What is needed is the grand vision to invest in and integrate exposomic science into public health and clinical medicine. This is the final piece of the puzzle. Once we understand our exposome and integrate it with our genome, we will finally understand why and how chronic diseases have become so common and how we can start to reverse their trends in society.

Dr Robert Wright is a pediatrician, medical toxicologist, environmental epidemiologist and director of the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai

See the original post:

New year health kicks are great but your environment is also vital - The Guardian

Astellas Pharma recentlyagreed to acquire Audentes Therapeutics, a move it expects will result in faster development of potentially best-in-class therapies for rare neuromuscular diseases, including muscular dystrophy (MD).

Audentes vectorized exon-skipping technology which uses a modified adeno-associated virus (AAV) vector to allow cells to skip over mutated sections of genes will complement Astellas own work, Kenji Yasukawa, president and CEO of Astellas, said in a press release.

Recent scientific and technological advances in genetic medicine have advanced the potential to deliver unprecedented and sustained value to patients, and even to curing diseases with a single intervention, Yasukawa said.

Audentes has developed a robust pipeline of promising product candidates which are complementary to our existing pipeline, including its lead program AT132, he added. By joining together with Audentes talented team, we are establishing a leading position in the field of gene therapy with the goal of addressing the unmet needs of patients living with serious, rare diseases.

The technology uses the modified AAV vector to deliver small molecules antisense oligonucleotides complementary to the RNA sequence of a gene of interest, which allow cells to skip over mutated exons while they are producing proteins.

Exons are the coding regions of genes that provide instructions to make proteins.

Audentes had started developing several therapies for Duchenne muscular dystrophy (DMD) based on its exon-skipping technology. These include AT702, AT751 and AT753.

All three treatment candidates use the same AAV delivery vector. However, as they target different DMD gene exons, the potential therapies are intended for distinct subgroups of patients. AT702 is designed to skip exon 2 and is meant for those who either have duplications in exon 2 or mutations in exons 1-5. AT751 is designed for those with mutations in exon 51, and AT753 for people with alterations in exon 53.

Audentes had also started developing and testing AT466, an experimental treatment for myotonic dystrophy type 1.

The acquisition also gives Astellas direct access to AT132, Audentes lead gene therapy candidate for the treatment ofX-linked myotubular myopathy.

AT132 uses an AAV8 viral vector to deliver a functional copy of the MTM1 gene to muscle cells. This enables the production of myotubularin, an important enzyme for the development and maintenance of muscle cells.

Matthew R. Patterson, chairman and CEO of Audentes, said his company is very pleased with the agreement. With its focus on innovative science and a global network of research, development and commercialization resources, we believe that operating as part of the Astellas organization optimally positions us to advance our pipeline programs and serve our patients, he said.

Under the terms of the agreement, Audentes will become an independent subsidiary of Astellas and will have access to scientific resources to accelerate the development and manufacturing of the combined product pipeline. The transaction, worth $3 billion, is expected to take place early this year.

Joana is currently completing her PhD in Biomedicine and Clinical Research at Universidade de Lisboa. She also holds a BSc in Biology and an MSc in Evolutionary and Developmental Biology from Universidade de Lisboa. Her work has been focused on the impact of non-canonical Wnt signaling in the collective behavior of endothelial cells cells that make up the lining of blood vessels found in the umbilical cord of newborns.

Total Posts: 42

Jos is a science news writer with a PhD in Neuroscience from Universidade of Porto, in Portugal. He has also studied Biochemistry at Universidade do Porto and was a postdoctoral associate at Weill Cornell Medicine, in New York, and at The University of Western Ontario in London, Ontario, Canada. His work has ranged from the association of central cardiovascular and pain control to the neurobiological basis of hypertension, and the molecular pathways driving Alzheimers disease.

Here is the original post:

New MD Treatments the Main Goal of Astellas, Audentes Merger - Muscular Dystrophy News

We look forward to hosting our precision medicine conference for the second year in a row, said Phil Talamo, president of PER. This meeting is designed to take a targeted approach to treatment, focusing on how biomarkers and testing strategies can personalize care to patients, often times in a tumor agnostic setting.

Across a two-day, pan-tumor symposium, expert faculty will cover the latest topics in solid and liquid tumors, including lung, breast, gastrointestinal, genitourinary, skin cancers and hematologic malignancies. The educational meeting will feature high-impact sessions and keynote lectures that will focus on practical takeaways regarding the latest updates in next-generation sequencing, liquid biopsy and cytogenetic testing. The program will review updates in targeted treatment, including tumor-agnostic indications based solely on genomic markers and other biomarkers. The tumor board overall will emphasize the role of advanced genetic panel testing and the use of targeted therapies, with a focus on data that is most relevant to patient care.

For more information and to register, click here.

About Physicians Education Resource (PER)

Since 1995, PER has been dedicated to advancing cancer care through professional education and now advances patient care and treatment strategies on a wide variety of chronic illnesses and diseases. In 2016, PER initiated continuing medical education (CME) programming in the cardiovascular and endocrinology areas. While expanding into topics outside of oncology, PER stands as the leading provider of live, online and print CME activities related to oncology and hematology. The high-quality, evidence-based activities feature leading distinguished experts who focus on the application of practice-changing advances. PER is accredited by the Accreditation Council for Continuing Medical Education and the California Board of Registered Nursing. PER is a brand of MJH Life Sciences, the largest privately held, independent, full-service medical media company in North America dedicated to delivering trusted health care news across multiple channels.

View source version on businesswire.com: https://www.businesswire.com/news/home/20200109005679/en/

View post:

Physicians' Education Resource Presents the 2nd Annual Precision Medicine Symposium in New York City - BioSpace

An Amish boy and girl walking along the road near Paradise, Pennsylvania Photo: Getty Images

In a new paper this week, doctors at the Mayo Clinic say theyve uncovered the cause of a mysterious heart condition that had suddenly killed over a dozen young, healthy members of a tight-knit Amish community. The culprit? A previously undiscovered genetic mutation that runs in families.

Study author Michael Ackerman, a cardiologist and professor at the Mayo Clinic College of Medicine and Science, is also director of the Mayo Clinic Windland Smith Rice Sudden Death Genomics Laboratory. For years, the lab has investigated cases in which seemingly healthy people died with no clear cause, hoping to unearth new ways our genes can send us to an early grave. In many of these cases, peoples hearts simply stopped beating, a condition otherwise known as cardiac arrest.

According to Ackerman, the journey to unraveling this particular mystery was a long one.

The medical examiner first contacted me and my research team over 15 years ago, after the deaths of two Amish siblings during recreational play over four months time, Ackerman told Gizmodo via email. For me, in situations like these, it is either foul play or genetic. [But] there was no way based on interviews with the family that this was foul play, so we searched for the genetic cause of sudden cardiac death.

As is often the case with smaller, isolated communities of people, the Amish have more in common genetically with one another than people living in a typical modern community do with their neighbors. Unfortunately, the less genetically diverse a population is, the easier it is for harmful genetic conditions to emerge and be passed down to the next generation. These conditions are often recessive, meaning it takes having two copies of the unlucky genetic variationone inherited from each parentfor symptoms to show up. Those who carry just one copy of the bad variation usually end up with no health problems, and even if they have children with another carrier, theres only a 25 percent chance a child of theirs will have both copies.

From the start, Ackerman and his team suspected a recessive mutation could be responsible for what happened to the children, since their family tree had a history of closely related ancestors while the parents themselves seemed perfectly healthy. But their initial sweep failed to turn up potential clues.

Tragically, two more children in the family would later die of sudden cardiac arrest as well, six and eight years after the first deaths, respectively. All of them, no younger than 12, had been playing or exercising right before their deaths.

By the time of these newer deaths, though, genetic technology had advanced enough for the team to try looking again. In particular, they were now able to scan a persons entire exome, the bits of DNA that actually program our cells to make the building block proteins we need to live. And this time, they found a likely suspect: a duplication of DNA found in segments of the RYR2 gene as well as in another region that controls its expression.

The RYR2 gene helps regulate our heart muscles calcium release channels (CRC). These channels need to carefully manage the flow of calcium in and out of heart cells to keep the organ healthy and beating as it should during times of rest and stress alike. People are already known to have genetic mutations that can leave them with overactive CRCsa condition that also raises their risk of sudden cardiac death. But this specific mutation seems to create the opposite problem, leaving victims with too few CRCs.

As the team theorized, the children who had died all had two copies of the mutation, while the parents and unaffected siblings all had either one or no copies. They then came across a second large Amish family, unrelated to the first, that also had a history of healthy young people suddenly dying of or barely surviving cardiac arrest. And when the second family was tested, nearly all of those with two copies of the mutated gene had died or developed these symptoms.

The teams findings were published Wednesday in JAMA Cardiology.

Ultimately, through a combination of technology and tenacity, we found the answer, Ackerman said.

The mutation and the condition it causescoined calcium release channel deficiency syndrome by the teamstill needs to be studied by other researchers before it can be confirmed as a genuine disorder. But so far, 23 people have been identified with the mutation, with 18 having died, across the two families, while more relatives are being tested by the team. Ackerman said his teams work has been greatly appreciated and celebrated by the families.

The power of closurefiguring out the truth about what was behind all of these tragediesand claritybeing able to figure out who does and who does not have these markersis incredible, as you can imagine, he said.

Our genes usually influence our health insubtle ways. Even people who have a clearly troublesome mutation dont always become seriously sick. But conventional tests havent been able to tell when someone with the condition will have heart troubles. And given how quickly lethal it can be, Ackerman expects that affected individuals will need an implantable cardioverter-defibrillator that can intervene when the heart loses control of itself. More importantly, though, we can now find these people before its too late.

Although we could not save the lives of these precious children and teenagers and young adults, we now have a diagnostic biomarker such that no more deaths from CRC deficiency syndrome should have to ever occur again, Ackerman said.

Visit link:

A Genetic Mutation Is Responsible for Mysterious Deaths in the Amish Community, Researchers Say - Gizmodo

(Mainichi)

Some iPS cells for regenerative medicine, distributed by a stock project at Kyoto University's Center for iPS Cell Research and Application (CiRA), showed cancer-related genetic and chromosomal abnormalities when differentiated to the target cells, several sources close to the project revealed.

Some of the iPS cells, even those produced at the same time, showed various abnormalities while others did not, depending on the research institution they were distributed to, prompting experts to voice concerns over their safety. The CiRA has acknowledged the facts, and the cells that developed abnormalities were not used in patients.

The project stockpiles iPS cells provided by the same suppliers at the same time in a cell line. In clinical research and a trial, iPS cells and differentiated cells go through genome analysis, and are transplanted into mice to check whether they turn cancerous. It is then decided which cell line should be distributed to implementing agencies.

Of the 27 cell lines distributed since August 2015, test results were revealed for four. Of these, abnormalities were found in two cell lines. The two cell lines were distributed in several containers to two research institutions, respectively, and were differentiated to the same target cells at each institution.

For one of the cell lines, one institution found a genetic abnormality in relation to cancer, while the other found a numerical disorder in the chromosome. For the other cell line, one institution found a different genetic abnormality, while the other institution did not find any irregularities. Furthermore, the institution that found the abnormality did not find any problems in the cells kept in a different container.s

Genetic abnormalities included a high-risk abnormality, similar to those found in humans with cancer. When implanted in mice, abnormal tissue growth that cannot be seen with normal cells was confirmed.

"No matter what kind of cell, an error could occur during the process of cultivation and differentiation," said specially appointed professor and manufacturing supervisor Masayoshi Tsukahara of the iPS cell stock project. He explained, "There's no other choice but to conduct careful tests before putting them to use."

Several experts in Japan, however, expressed concerns that safety cannot be ensured if test results vary depending on containers.

Michael Snyder, professor at Stanford University's School of Medicine and the director of the Center for Genomics and Personalized Medicine, pointed to the need to evaluate the matter in an open discussion.

(Japanese original by Momoko Suda, Science & Environment News Department)

Read the original here:

Kyoto Univ.-distributed iPS cells found with abnormalities after differentiation - The Mainichi

Youre unwell, you see a doctor, they prescribe you a medicine and you take it. But how exactly is that drug having an effect? What is its mechanism of action? Drugs exhibit their effects through specific protein-target interactions.

But in some cases, there may not be a treatment available. In approximately 30% of cases, drugs fail during clinical development, and toxicity which can be caused by off-target binding is often to blame.

Andrew Lynn, Chief Executive Officer at Fluidic Analytics discusses why understanding protein-target interactions is so important, the common challenges researchers face when attempting to determine these interactions, and touches on the relationship between the drug "attrition rate" crisis and the off-target effects of drugs.

Laura Lansdowne (LL): Could you discuss the importance of understanding proteintarget interactions in drug discovery, and the implications of not knowing your target?Andrew Lynn (AL): Understanding proteintarget interactions is crucial we are talking about the difference between finding a lifesaving drug/therapy and wasting hundreds of millions of dollars developing a drug with the wrong mechanism of action.A recent paper from Jason Sheltzers group showed that ten anticancer drugs undergoing clinical trials had a completely different mechanism of action from the one originally attributed to them. Briefly, when the protein targeted by each of the drugs was removed from cancer cells, the group expected the drugs to stop working. But what they found was that the drugs continued to work as normal and thus had to be working through off-target binding.This is crucial because it means potentially there are many more drugs out there that are working through off-target binding; it also means that many other drug candidates that have previously been disregarded may have unrecognized promise. This problem is about to become even more acute as research expands into conditions with difficult targets like Alzheimer's disease.The way in which we discover the exact mechanism of action between proteins and potential drug candidates needs better technologies for characterizing on-target and off-target interactions We cannot discover new information relying solely on technologies that have fallen short for decades.LL: What challenges do drug discovery researchers face when trying to identify targetprotein interactions?AL: Drug discovery and development is a lengthy, complex and costly process with a high degree of uncertainty whether a drug will succeed. The two biggest challenges are: First, not understanding the pathophysiology of many disorders, such as neurodegenerative disorders, which makes target identification challenging. Second, the lack of validated diagnostic and therapeutic biomarkers to objectively detect and measure biological states.At the heart of both challenges is the ability to characterize protein-drug target interactions. Unfortunately, the methods currently employed by researchers to do this research are outdated.

An example of this can be seen when scientists try to characterize interactions involving intrinsically disordered proteins (IDPs) such as the ones associated with Parkinsons disease. Current characterization methods modify proteins by fixing them to a surface or putting them in artificial environments. So, its no surprise that many drugs are great at targeting proteins with these modifications but poor at targeting these same proteins as they exist in vivo in solution and not tethered to an artificial surface.

This is why were building new tools and methods for researchers to more accurately characterize binding events in solution: to better understand how drugs interact with their protein targets in their native environment.

LL: What is microfluidic diffusional sizing and how can this be used to measure the binding affinity of proteinprotein interactions?AL: Microfluidic diffusional sizing (MDS) characterizes proteins and their interactions in solution based on the size (or more specifically hydrodynamic radius) of proteins and protein complexes as they diffuse within a microfluidic laminar flow. Characterizing in solution avoids artefacts from surfaces or matrices; gathering information about size to give crucial insights into stoichiometry, on- and off-target binding, oligomerization and folding.

MDS can be used to measure binding affinity by tracking changes in the size of a protein as it binds at different concentrations. The size of the complex can also give a strong indication of whether the protein is forming a protein-target complex at the expected size (on-target binding) or something with a completely different or unexpected size (off-target binding). A major additional advantage of MDS is that, because of the absence of surfaces or matrices, it can be used to characterize binding involving difficult targets such as intrinsically disordered proteins and membrane proteins.

LL: Could you discuss the relationship between the drug "attrition rate" crisis and the off-target effects of drugs?AL: Compound failure rates due to toxicity before human testing is very high. A recent review from a top-20 pharma company cited toxicity as the reason why, between 2005-2010, 82% of drugs were rejected at the preclinical stage and 35% in phase 2a. Overall, concerns surrounding toxicity account for as much as 30% of drug attrition occurring during the clinical stage of development.For many potential drugs, toxicity is due to off-target binding. By employing new methods to characterize drug candidates binding to protein targets in native conditions, we can identify off-target binding more effectively. This could help save billions of dollars in development costs and reduce the attrition rate we are currently facing.

LL: There has currently been very limited success in the development of effective therapies for Alzheimers disease (AD). Could you touch on some of the successes and highlight the molecules of interest in AD as well as the challenges related to their study.AL: One recent success is the anti-amyloid drug, aducanumab. After Biogen re-examined the data from the clinical trials, they found that exposure to high doses of Aducanumab reduced clinical decline in patients exhibiting early stages of Alzheimers disease.If approved, aducanumab would become the first therapy to slow the cognitive decline that accompanies Alzheimer's disease. This a massive step forward and a much-needed source of hope for patients and their families.But aducanumab doesnt cure Alzheimers disease. A major challenge impeding the development of further AD drugs is the ability to understand the mechanism of action via which candidate drugs interact with targets. Amyloid- is known to be a particularly difficult-to-characterize peptide, and even aducanumab doesnt have a well-understood mechanism of action. Any breakthroughs in being able to characterize how it or other Alzheimers disease drugs interact with difficult targets would be a major breakthrough in drug development.However, the majority of Alzheimers patients do not carry the dominantly inherited genetic mutation for the disease, and we dont know why amyloid proteins aggregate within their brains.

It follows that there wont be a single cause but rather many causes. Thus, the common consensus is that there wont be a single miracle drug that cures Alzheimers disease for everyone.

Andrew Lynn was speaking with Laura Elizabeth Lansdowne, Senior Science Writer, Technology Networks.

Read more:

The Importance of Understanding TargetProtein Interactions in Drug Discovery - Technology Networks

For all of the hype surrounding gene therapy and gene editing, the precision genetic medicine approach that turned in the best 2019 may have been RNA interference (RNAi). The gene-silencing technique earned its first regulatory approval for a novel targeted delivery method. That may not sound like much to get excited about, but it promises to open up numerous high-value opportunities for RNAi drug developers.

The approval, coupled with promising early-stage clinical results and massive partnership deals, explains why Arrowhead Pharmaceuticals (NASDAQ:ARWR) and Dicerna Pharmaceuticals (NASDAQ:DRNA) erupted higher in 2019. The RNAi drug developers saw their market valuations increase by 450% and 106%, respectively, last year.

While both companies have promise, thepharma stocks are likely to fall in early 2020. What does that mean for investors with a long-term mindset?

Image source: Getty Images.

Shares of Arrowhead Pharmaceuticals had a pretty good first nine months of 2019, but the most impressive gains came in the fourth quarter. The RNAi stock gained heading into the American Association for the Study of Liver Diseases (AASLD) Annual Meeting in November. Investors were eagerly awaiting the results of two drug combinations being developed to treat chronic hepatitis B (CHB) by Johnson & Johnson (NYSE:JNJ) subsidiary Janssen.

The results lived up to the hype. The most impressive data came from a triple combination of an RNAi drug from Arrowhead Pharmaceuticals (now called JNJ-3989), an antiviral drug from Johnson & Johnson (JNJ-6379), and a nucleos(t)ide analog (NA). After 16 weeks of treatment, all 12 individuals in the study achieved at least a 90% reduction in two biomarkers of hepatitis B virus activity.

Investors gobbled up shares of Arrowhead Pharmaceuticals because the triple combination appears to be the industry's best hope for developing the first functional cure for CHB (although it can't be called a functional cure just yet).

Additionally, the RNAi drug candidate in the triple combination is based on a targeted delivery platform called TRiM. The approach is simple: The gene-silencing payload is attached to a special sugar that's absorbed by the liver. Since many RNAi drug candidates need to interact with DNA in liver cells, and the sugars are easily metabolized by the liver (improving safety over prior-generation lipid nanoparticle delivery vehicles), it's a perfect pairing.

It helps that just a few weeks after AASLD, Givlaari from Alnylam Pharmaceuticals (NASDAQ:ALNY)became the first RNAi drug candidate based on a conjugated-sugar delivery method to earn regulatory approval. It also helps that Dicerna Pharmaceuticals landed two massive partnerships in the fourth quarter of 2019 -- both based on its own conjugated-sugar delivery platform. Following those deals, there's now considerable overlap between the pipelines of Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals, which are both all-in on targeted delivery.

RNAi Developer

Partner, Indication

Financial Terms

Arrowhead Pharmaceuticals

Johnson & Johnson, hepatitis B

$175 million up front, $75 million equity investment, up to $1.6 billion in milestone payments, royalties

Arrowhead Pharmaceuticals

Johnson & Johnson, undisclosed

Up to $1.9 billion in total milestone payments for up to three additional drug candidates, royalties

Arrowhead Pharmaceuticals

Amgen, cardiovascular disease

$35 million up front, $21.5 million equity investment, up to $617 million in milestone payments, royalties

Dicerna Pharmaceuticals

Roche, hepatitis B

$200 million up front, up to $1.47 billion in milestone payments, royalties

Dicerna Pharmaceuticals

Novo Nordisk, various liver-related cardio-metabolic diseases

$175 million up front, equity investment of $50 million, an additional $75 million over the first three years, up to $357.5 million per drug candidate, royalties

Data source: Press releases, filings with the Securities and Exchange Commission.

Despite all of the progress from both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals in 2019, both companies are likely to fall back to Earth a bit following giant run-ups.

Consider that Arrowhead Pharmaceuticals is valued at $6.3 billion at the start of 2020. The company's most advanced drug candidate, ARO-AAT, recently began dosing patients in a phase 2/3 trial in a rare genetic liver disease associated with alpha-1 antitrypsin (AAT or A1AT) deficiency. While that study can be used for a new drug application (NDA), and the drug candidate could achieve over $1 billion in peak annual sales, that alone doesn't support a $6.3 billion valuation.

Meanwhile, the triple combination in CHB could support a market valuation well above $6 billion, especially if it proves to be a functional cure. The drug candidate could eventually earn peak annual sales of over $10 billion in that scenario. But the recent gains were spurred by results in only 12 individuals after 16 weeks of follow-up. A phase 2b trial now underway will enroll 450 patients and follow them for two years. In other words, there's plenty of time for investors to take some gains off the table.

Dicerna Pharmaceuticals is valued a little more reasonably, at just $1.5 billion, but it has only one drug candidate in mid- or late-stage clinical trials. The pipeline programs at the center of recent deals with Roche and Novo Nordisk are still in preclinical development or phase 1 studies; there's little to no clinical data from the programs for investors to survey. While the business will be flush with cash after receiving up-front payments in the coming months, there's a lot of work to be done.

To be clear, both Arrowhead Pharmaceuticals and Dicerna Pharmaceuticals hold a lot of promise. Targeted delivery of RNAi drug payloads into the liver could open up considerable opportunities to treat -- for the first time, in some cases -- rare diseases, viral infections, and cardiovascular ailments. Both companies have even demonstrated early work to target gene-silencing payloads to other cell types, such as muscle tissues, which may open up additional avenues for drug discovery and development.

However, these two RNAi stocks have fallen 10.7% and 12.3%, respectively, since Dec. 3 -- and both are likely to fall a bit further in early 2020. If and when that occurs, investors may want to give each stock, especially Arrowhead Pharmaceuticals, a closer look.

Continue reading here:

These 2 Stocks Will Fall After the New Year - Motley Fool

James Lu, M.D., PH.D.Co-founder & Senior Vice President of Applied GenomicsHelix

James is a co-founder and SVP of Applied Genomics at Helix, a population genomics company with a mission to empower every person to improve their life through DNA. Helix is accelerating the integration of genomic data into clinical care and broadening the impact of large-scale population health programs by providing comprehensive expertise in DNA sequencing, bioinformatics, and individual engagement. Powered by our proprietary Exome+assaya panel-grade exome enhanced by more than 300,000 informative non-coding regionsHelix partners with health systems to provide a scalable solution which enables the discovery of medically relevant, potentially life-saving, genetic information. Additionally, Helix offers a suite of DNA-powered products for continued individual engagement and discovery.

At Helix, James is responsible for the scientific teams which include bioinformatics, laboratory operations, regulatory, quality, translational research and policy teams.

Prior to Helix, James was a faculty member at Duke University where he focused on translational genomics and machine learning methodologies for electronic medical records. James has also explored a broad range of research topics in population genetics, Mendelian genomics, and computational psychiatry and has published dozens of papers in journals such as Nature, the New England Journal of Medicine and the Journal of Machine Learning Research.

More here:

Webinar: How Providers are Harnessing the Power of Genomics to Improve Community Health - ModernHealthcare.com

January 03, 2020 -Maximum Life Foundation (MaxLife), a non-profit organization focused on aging research, is providing a promising free gene therapy for ten patients with Alzheimers disease.

According to the Alzheimers Association, Alzheimers disease is the sixth leading cause of death in the US. Over five million Americans have the condition, leading to costs of $277 billion a year.

With this gene therapy, researchers have seen improvements in Alzheimers symptoms and the recovery of normal brain functions in experiments with mice. In human cell experiments, the therapy had the same effects through the rejuvenation of microglia, the brains first line of defense against infection, and neurons.

In August 2018, a patient received a low dose of the therapy with no adverse side effects. To date, the patients disease hasnt progressed.

MaxLife will grant 100 percent of the therapy costs to help bring pioneering gene therapy to cure this disease and make Alzheimers disease a thing of the past, said David Kekich, MaxLifes CEO.

Studies have proven that aging is the leading factor in many life-threatening diseases, including Alzheimers. This new gene therapy aims to treat the cellular degeneration caused by aging.

The new treatment is offered by Integrated Health Systems, a gene therapy facilitator that is seeking to treat other adult aging-related diseases with no known cure, including sarcopenia, chronic kidney disease, and atherosclerosis.

This technology could halt many of the big age-associated killers in industrialized countries, said Kekich. Compassionate care helps patients with no other option to get access to experimental therapies that may benefit both themselves and society as a whole.

Other healthcare organizations have stressed the need to leverage gene therapies and precision medicine to improve treatment for Alzheimers and other diseases. A recent study published in Frontiers in Aging Neuroscience discussed how precision medicine tactics will help improve cognitive disease treatment.

Taking a precision medicine approach, the question is no longer Does treatment work? but Who does treatment work for? Identifying the characteristics of non-responders becomes as important as responders in understanding the impact of a particular intervention, the team said.

Such an approach may result in considerable health benefits by allowing more effective selection of individuals for treatments based ona prioriknown profiles of disease risk and their potential response to treatment.

Researchers at Massachusetts General Hospital (MGH) also recently discovered that certain genetic variants may help protect individuals against Alzheimers disease, a finding that could hold important implications for precision medicine therapies.

The team studied a patient who carried a mutation in a gene known to cause early onset Alzheimers but didnt show signs of mild cognitive impairment until her seventies. This is nearly three decades after the typical age of onset. Evaluating this patient, and patients like her, could help researchers understand more about the progression of Alzheimers.

This single case opens a new door for treatments of Alzheimers disease, based more on the resistance to Alzheimers pathology rather than on the cause of the disease. In other words, not necessarily focusing on reduction of pathology, as it has been done traditionally in the field, but instead promoting resistance even in the face of significant brain pathology, said Yakeel T. Quiroz, PhD, clinical neuropsychologist and neuroimagingresearcher at MGH.

With the new gene therapy, MaxLife will add to the growing body of research exploring the use of precision medicine and genetics in chronic disease treatment.

If we can prove a benefit to patients that have no other option now, we can potentially treat Alzheimers disease in people in early to mid-stage Alzheimers, finally creating effective medicine at the cellular level, states Kekich. If successful, this treatment could potentially be used on other diseases such as Parkinsons and ALS.

To apply for a free therapy or for more information, click here.

Excerpt from:

Free Gene Therapy Available for Patients with Alzheimer's - HealthITAnalytics.com

He Jiankui, a Chinese researcher shown here at a conference last year in Hong Kong, has been sentenced to three years in prison. Kin Cheung/AP hide caption

He Jiankui, a Chinese researcher shown here at a conference last year in Hong Kong, has been sentenced to three years in prison.

Updated at 1:30 p.m. ET

A Chinese scientist who shocked the medical community last year when he said he had illegally created the world's first gene-edited babies has been sentenced to three years in prison by a court in southern China.

He Jiankui announced in November 2018 that he had used a powerful technique called CRISPR on a human embryo to edit the genes of twin girls. He said he modified a gene with the intention of protecting the girls against HIV, the virus that causes AIDS. Many scientists expressed concerns about possible unintended side effects of the genetic changes that could be passed down to future generations.

Last fall, He also indicated there might be another pregnancy involving a gene-edited embryo. The court indicated that three genetically edited babies have been born.

The closed court in Shenzhen found He and two colleagues guilty of illegal medical practice by knowingly violating the country's regulations and ethical principles with their experiments, Xinhua news agency reported. It also ordered He to pay a fine of about $430,000.

He's colleagues, Zhang Renli and Qin Jinzhou, were handed lesser sentences and fines.

"None of the three defendants acquired doctor's qualifications. [They] craved fame and fortune and deliberately went against the country's regulations on scientific research and medical management. [They] went beyond the bottom lines of scientific research and medical ethics," the court stated, according to the South China Morning Post.

He has defended his controversial work by saying that it will help families. "I understand my work will be controversial," he said, as NPR's Rob Stein reported. "But I believe families need this technology. And I am willing to take the criticism for them."

At the time, scientists had previously genetically modified human embryos, but none had publicly claimed to have implanted embryos in a woman's womb in an experiment that resulted in human babies.

Chinese police detained He in January and, as the Post reported, an initial investigation concluded that he "organised a project team that included foreign staff, which intentionally avoided surveillance and used technology of uncertain safety and effectiveness to perform human embryo gene-editing activity with the purpose of reproduction, which is officially banned in the country."

The gene that He edited, CCR5, is known as a pathway for HIV to infect immune system cells. But as Stein notes, research carried out since He's stunning announcement has suggested that the genetic changes he made could cause more harm than good to the babies' health.

A study in Nature Medicine analyzed the DNA of more than 400,000 people and found that the changes that He made could make people more vulnerable to viruses such as West Nile and influenza.

"This is a lesson in humility," George Daley, the dean of the Harvard Medical School, told Stein. "Even when we think we know something about a gene, we can always be surprised and even startled, like in this case, to find out that a gene we thought was protective may actually be a problem."

Marcy Darnovsky, the executive director of the Center for Genetics and Society, said in an email to NPR that He's "reckless and self-serving acts should highlight the broader and deeper risks and the pointlessness of any proposal to use gene editing in human reproduction."

William Hurlbut, a scientist and bioethicist at Stanford who had attempted to persuade He (who is nicknamed JK) not to do the experiment, called his arrest a "sad story."

"Everyone lost in this (JK, his family, his colleagues, and his country), but the one gain is that the world is awakened to the seriousness of our advancing genetic technologies," Hurlbut said in an emailed statement. "I feel sorry for JK's little family though I warned him things could end this way, but it was just too late."

See the article here:

Chinese Researcher Who Created Gene-Edited Babies Sentenced To 3 Years In Prison - NPR

Hemophilia. Cystic fibrosis. Duchenne muscular dystrophy. Huntingtons disease. These are just a few of the thousands of disorders caused by mutations in the bodys DNA. Treating the root causes of these debilitating diseases has become possible only recently, thanks to the development of genome editing tools such as CRISPR, which can change DNA sequences in cells and tissues to correct fundamental errors at the sourcebut significant hurdles must be overcome before genome-editing treatments are ready for use in humans.

Enter the National Institutes of Health Common Funds Somatic Cell Genome Editing (SCGE) program, established in 2018 to help researchers develop and assess accurate, safe and effective genome editing therapies for use in the cells and tissues of the body (aka somatic cells) that are affected by each of these diseases.

Todaywith three ongoing grants totaling more than $6 million in research fundingDuke University is tied with Yale University, UC Berkeley and UC Davis for the most projects supported by the NIH SCGE Program.

In the 2019 SCGE awards cycle, Charles Gersbach, the Rooney Family Associate Professor of Biomedical Engineering, and collaborators across Duke and North Carolina State University received two grants: the first will allow them to study how CRISPR genome editing affects engineered human muscle tissues, while the second project will develop new CRISPR tools to turn genes on and off rather than permanently alter the targeted DNA sequence. This work builds on a 2018 SCGE grant, led by Aravind Asokan, professor and director of gene therapy in the Department of Surgery, which focuses on using adeno-associated viruses to deliver gene editing tools to neuromuscular tissue.

There is an amazing team of engineers, scientists and clinicians at Duke and the broader Research Triangle coalescing around the challenges of studying and manipulating the human genome to treat diseasefrom delivery to modeling to building new tools, said Gersbach, who with his colleagues recently launched the Duke Center for Advanced Genomic Technologies (CAGT), a collaboration of the Pratt School of Engineering, Trinity College of Arts and Sciences, and School of Medicine. Were very excited to be at the center of those efforts and greatly appreciate the support of the NIH SCGE Program to realize this vision.

For their first grant, Gersbach will collaborate with fellow Duke biomedical engineering faculty Nenad Bursac and George Truskey to monitor how genome editing affects engineered human muscle tissue. Through their new project, the team will use human pluripotent stem cells to make human muscle tissues in the lab, specifically skeletal and cardiac muscle, which are often affected by genetic diseases. These systems will then serve as a more accurate model for monitoring the health of human tissues, on-target and off-target genome modifications, tissue regeneration, and possible immune responses during CRISPR-mediated genome editing.

Currently, most genetic testing occurs using animal models, but those dont always accurately replicate the human response to therapy, says Truskey, the Goodson Professor of Biomedical Engineering.

Bursac adds, We have a long history of engineering human cardiac and skeletal muscle tissues with the right cell types and physiology to model the response to gene editing systems like CRISPR. With these platforms, we hope to help predict how muscle will respond in a human trial.

Gersbach will work with Tim Reddy, a Duke associate professor of biostatistics and bioinformatics, and Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor in Probiotics Research at North Carolina State University, on the second grant. According to Gersbach, this has the potential to extend the impact of genome editing technologies to a greater diversity of diseases, as many common diseases, such as neurodegenerative and autoimmune conditions, result from too much or too little of certain genes rather than a single genetic mutation. This work builds on previous collaborations between Gersbach, Barrangou and Reddy developing both new CRISPR systems for gene regulation and to regulate the epigenome rather than permanently delete DNA sequences.

Aravind Asokan leads Dukes initial SCGE grant, which explores the the evolution of next generation of adeno-associated viruses (AAVs), which have emerged as a safe and effective system to deliver gene therapies to targeted cells, especially those involved in neuromuscular diseases like spinal muscular atrophy, Duchenne muscular dystrophy and other myopathies. However, delivery of genome editing tools to the stem cells of neuromuscular tissue is particularly challenging. This collaboration between Asokan and Gersbach builds on their previous work in using AAV and CRISPR to treat animal models of DMD.

We aim to correct mutations not just in the mature muscle cells, but also in the muscle stem cells that regenerate skeletal muscle tissue, explainsAsokan. This approach is critical to ensuring long-term stability of genome editing in muscle and ultimately we hope to establish a paradigm where our cross-cutting viral evolution approach can enable efficient editing in multiple organ systems.

Click through to learn more about the Duke Center for Advanced Genomic Technologies.

More:

Duke Researchers Garner Over $6 Million in NIH Funding to Fight Genetic Diseases - Duke Today

NEW YORK Nam Bui has a piece of advice he wished he could share with more cancer patients: try to find a clinical trial.

Still, the Stanford University hematologist, academic oncologist, and medical oncology researcher recognizes the many obstacles to enrollment from geography to time-consuming trial criteria assessments. Not only is it difficult for clinicians to keep tabs on all of the trials open at a center at any given time, he argued, but the process of matching a patient to a trial can be time consuming.

Premium Access gives you: Full site access Interest-based email alerts Access to archives Never miss another important industry story.

Try Premium Access now.

You may already have institutional access!

Check if I qualify.

Already a Precision Oncology News or 360Dx or GenomeWeb Premium member?Login Now.

*Before your trial expires, well put together a custom quote with your long-term premium options.

Continued here:

Stanford Team Proposes Automated Clinical Trial Accrual Strategy, Increased Trial Annotation - Precision Oncology News

Treating 75,000 patients a year, the center has become among the top five busiest in the country. It receives $177 million in research funding and conducts more than 500 clinical trials each year, giving patients access to developing treatments.

Four satellite Siteman Cancer Centers have opened across the St. Louis region, with a fifth opening this month in the Metro East.

Alvin Siteman never stopped giving throughout the growth, which has led to some of the biggest discoveries in cancer research, and hes never stopped calling Eberlein his partner.

You know, Ruth and I are very private people, but almost everywhere I go I see my name, Siteman recently told Eberlein. I suppose I have you to thank for that.

In a rare combination, Siteman and Eberlein have been named the 2019 Citizens of the Year. The honor, usually given to just one person, is sponsored by the Post-Dispatch and selected by a committee of past winners.

I still joke with him. I say, Gee, Al, we werent even a start-up and you were willing to invest in us? What did you see? said Eberlein, 68. (Siteman, 91, has yet to grant any media requests for interviews or photos.) For him, it was a passion.

Eberlein and Siteman can attribute their successful partnership to similar trajectories of hard work, passion and curiosity.

Here is the original post:

Dr. Timothy Eberlein and Alvin Siteman named Citizens of the Year 2019 - STLtoday.com

For all of the wondrous potential of immunotherapies, there have been some notable obstacles in the early goings. Engineering immune cells to attack cancerous tumors can lead to solid results shortly after administering a dose, but for many patients the effects wear off once rapidly mutating tumor cells acquire new defense mechanisms.

Cellectis (NASDAQ:CLLS) thinks it may have a partial solution. In mid-November, the gene editing company published the results from a proof of concept study for its "smart" immunotherapy approach. Is the technique the future of cellular medicine?

Image source: Getty Images.

Today, cellular oncology therapies genetically engineer immune cells to bolster their safety and efficacy as a cancer treatment. There are T cells, natural killer (NK) cells, tumor infiltrating lymphocytes (TILs), and others. They're often engineered with chimeric antigen receptors (CARs) or T cell receptors (TCRs), which allow them to home in on and suppress specific genes in cancer cells.

While current-generation CAR T cells or CAR NK cells are capable of mounting formidable attacks on tumors at first, treatment responses aren't durable for all patients. That's because cancer cells mutate to rely on different proliferation genes, or secrete new molecules into the tumor microenvironment that neutralize immune cells. Meanwhile, overstimulating the immune system can reduce the potency of immune cells and lead to devastating side effects, such as cytokine release syndrome.

That prompted Cellectis to design "smart" CAR T cells capable of adapting to changes in the tumor microenvironment. In a proof of concept study, the company utilized synthetic biology concepts to rewire genetic circuits in three different genes of the initial T cells.

One edit made the immunotherapy more potent, but in a controlled manner to reduce off-target toxicity. The other two edits imbued CAR T cells with the ability to secrete inflammatory proteins inside the tumor microenvironment in proportion to the concentration of cancer cells.

In other words, the smart CAR T cells only asked for help from the rest of the immune system when it was needed most, which increased the anti-tumor activity of treatment and made native immune cells less likely to become neutralized. That should reduce the likelihood of triggering cytokine release syndrome, the most common (and potentially fatal) side effect of cellular medicines, which is caused by high concentrations of immune cells.

The study was conducted in mice, which means the safety and efficacy observations can't be extrapolated into humans. But that wasn't the point. The proof of concept demonstrates that the basic idea of engineering tightly controlled genetic circuits into immunotherapies is feasible. It could even allow multiple genetic circuits of the same drug candidate to be tested against one another in parallel, hastening drug development and lowering costs. Is it the inevitable future of cellular medicine?

Image source: Getty Images.

Gene editing tools are required to engineer immune cells. In fact, immunotherapies are the lowest hanging fruit for gene editing technology platforms today. It's simply easier to engineer immune cells in the lab (ex vivo) than it is to engineer specific cell types in the complex environment of the human body (in vivo).

That explains why nearly every leading gene editing company has immunotherapy programs in its pipeline. Coincidentally, all of the leading drug candidates in the industry pipeline are off-the-shelf CAR T cells engineered to treat CD19 malignancies such as non-Hodgkin's lymphoma (NHL) and B-acute lymphoblastic leukemia (B-ALL), regardless of the gene editing approach used. The smart CAR T cells designed by Cellectis targeted CD22 malignancies, but the approach could be adapted to CD19 antigen.

Developer(s)

Drug Candidate

Gene Editing Approach

Development Status

Cellectis and Servier

UCART19

TALEN

Phase 2

Precision BioSciences (NASDAQ:DTIL)

PCAR0191

ARCUS gene editing

Phase 1/2

CRISPR Therapeutics (NASDAQ:CRSP)

CTX110

CRISPR-Cas9

Phase 1/2

Sangamo Therapeutics (NASDAQ:SGMO) and Gilead Sciences (NASDAQ:GILD)

KITE-037

Zinc finger nuclease

Preclinical

Data source: Company websites.

Will these companies eventually turn to "smart" immunotherapies with regulated genetic circuits? It does seem inevitable, especially if the approach can reduce or eliminate cytokine release syndrome and enable more durable responses.

For example, Cellectis reported that all seven patients taking part in the phase 1 trial of UCART19 suffered from at least grade 1 cytokine release syndrome, which caused complications that led to the death of one patient. Five of the seven patients achieved molecular remission, but one relapsed (and remained alive) and one died. To be fair, all patients taking part in the trial had advanced, heavily pretreated B-ALL.

Precision BioSciences has encountered similar obstacles in an ongoing phase 1/2 trial of PBCAR0191. The company's lead drug candidate was administered to nine patients with NHL or B-ALL. Three cases of cytokine release syndrome were reported, but all were manageable. Seven responded to treatment, including two that achieved a complete response, but three eventually relapsed.

CRISPR Therapeutics recently began dosing patients with CTX110 in a phase 1/2 trial that will eventually enroll up to 95 individuals, but initial results won't be available until 2020. Sangamo Therapeutics and Kite Pharma, a subsidiary of Gilead Sciences, are plowing ahead with zinc fingers,but are still in preclinical development.

Investors seem pleased with most of these gene editing stocksright now. After all, despite the obstacles, current-generation cellular medicines are delivering impressive results in patient populations with relatively few options. But upcoming data readouts could easily differentiate the pack. That could increase the need to invest in augmented capabilities, such as smart immunotherapies.

There's plenty of untapped potential in cellular medicine. Today, companies are developing drug candidates with engineered CARs and TCRs designed to test hypotheses about the function of immunotherapies. As approaches find success, measured in safer and more durable responses, the next layer of complexity will be added in an effort to find even more successful therapies. And the cycle will continue.

Therefore, it seems inevitable that the field of cellular medicine will turn to smart immunotherapies with more complex genetic edits, much like the field quickly embraced the need for engineered immune cells and off-the-shelf manufacturing processes. That said, the immediate focus for Cellectis and its peers is building a stable foundation -- and those efforts have only just begun.

View original post here:

Did Cellectis Just Provide a Glimpse of the Future of Cellular Medicine? - The Motley Fool

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States. Meredith Rizzo/NPR hide caption

Victoria Gray, who has sickle cell disease, volunteered for one of the most anticipated medical experiments in decades: the first attempt to use the gene-editing technique CRISPR to treat a genetic disorder in the United States.

When Victoria Gray was just 3 months old, her family discovered something was terribly wrong.

"My grandma was giving me a bath, and I was crying. So they took me to the emergency room to get me checked out," Gray says. "That's when they found out that I was having my first crisis."

It was Gray's first sickle cell crisis. These episodes are one of the worst things about sickle cell disease, a common and often devastating genetic blood disorder. People with the condition regularly suffer sudden, excruciating bouts of pain.

"Sometimes it feels like lightning strikes in my chest and real sharp pains all over. And it's a deep pain. I can't touch it and make it better," says Gray. "Sometimes, I will be just balled up and crying, not able to do anything for myself.

Gray is now 34 and lives in Forest, Miss. She volunteered to become the first patient in the United States with a genetic disease to get treated with the revolutionary gene-editing technique known as CRISPR.

NPR got exclusive access to chronicle Gray's journey through this medical experiment, which is being watched closely for some of the first hints that changing a person's genes with CRISPR could provide a powerful new way to treat many diseases.

"This is both enormously exciting for sickle cell disease and for all those other conditions that are next in line," says Dr. Francis Collins, director of the National Institutes of Health.

"To be able to take this new technology and give people a chance for a new life is a dream come true," Collins says. "And here we are."

Doctors removed bone marrow cells from Gray's body, edited a gene inside them with CRISPR and infused the modified cells back into her system this summer. And it appears the cells are doing what scientists hoped producing a protein that could alleviate the worst complications of sickle cell.

"We are very, very excited," says Dr. Haydar Frangoul of the Sarah Cannon Research Institute in Nashville, Tenn., who is treating Gray.

Frangoul and others stress that it's far too soon to reach any definitive conclusions. Gray and many other patients will have to be treated and followed for much longer to know whether the gene-edited cells are helping.

"We have to be cautious. It's too early to celebrate," Frangoul says. "But we are very encouraged so far."

Collins agrees.

"That first person is an absolute groundbreaker. She's out on the frontier," Collins says. "Victoria deserves a lot of credit for her courage in being that person. All of us are watching with great anticipation."

This is the story of Gray's journey through the landmark attempt to use the most sophisticated genetic technology in what could be the dawn of a new era in medicine.

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe. Meredith Rizzo/NPR hide caption

The study took place at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, in Nashville, Tenn., one of 11 sites recruiting patients for the research in the U.S., Canada and Europe.

Life filled with pain

When I first meet her, Gray is in a bed at the TriStar Centennial Medical Center in Nashville wearing a hospital gown, big gold hoop hearings and her signature glittery eye shadow.

It's July 22, 2019, and Gray has been in the hospital for almost two months. She is still recovering from the procedure, parts of which were grueling.

Nevertheless, Gray sits up as visitors enter her room.

"Nice to meet y'all," she says.

Gray is just days away from her birthday, which she'll be celebrating far from her husband, her four children and the rest of her family. Only her father is with her in Nashville.

"It's the right time to get healed," says Gray.

Gray describes what life has been like with sickle cell, which afflicts millions of people around the world, including about 100,000 in the United States. Many are African American.

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company. Meredith Rizzo/NPR hide caption

In July, Gray was recovering after a medical procedure that infused billions of her own bone marrow cells back into her body after they had been modified using the gene-editing technique CRISPR. Her father, Timothy Wright (right), traveled from Mississippi to keep her company.

"It's horrible," Gray says. "When you can't walk or, you know, lift up a spoon to feed yourself, it gets real hard."

The disease is caused by a genetic defect that turns healthy, plump and pliable red blood cells into deformed, sickle-shaped cells. The defective cells don't carry oxygen well, are hard and sticky and tend to clog up the bloodstream. The blockages and lack of oxygen wreak havoc in the body, damaging vital organs and other parts of the body.

Growing up, Victoria never got to play like other kids. Her sickle cells made her weak and prone to infections. She spent a lot of time in the hospital, recovering, getting blood transfusions all the while trying to keep up with school.

"I didn't feel normal. I couldn't do the regular things that every other kid could do. So I had to be labeled as the sick one."

Gray made it to college. But she eventually had to drop out and give up her dream of becoming a nurse. She got a job selling makeup instead but had to quit that too.

The sickle-shaped cells eventually damaged Gray's heart and other parts of her body. Gray knows that many patients with sickle cell don't live beyond middle age.

"It's horrible knowing that I could have a stroke or a heart attack at any time because I have these cells in me that are misshapen," she says. "Who wouldn't worry?"

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says. Meredith Rizzo/NPR hide caption

Gray says she understands the risks involved in the treatment. "This gives me hope if it gives me nothing else," she says.

Gray married and had children. But she hasn't been able to do a lot of things most parents can, like jump on a trampoline or take her kids to sporting events. She has often had to leave them in the middle of the night to rush to the hospital for help.

"It's scary. And it affected my oldest son, you know, because he's older. So he understands. He started acting out in school. And his teacher told me, 'I believe Jemarius is acting out because he really believes you're going to die,' " Gray says, choking back tears.

Some patients can get help from drugs, and some undergo bone marrow transplants. But that procedure is risky; there's no cure for most patients.

"It was just my religion that kind of kept me going," Gray says.

An eager volunteer

Gray had been exploring the possibility of getting a bone marrow transplant when Frangoul told her about a plan to study gene editing with CRISPR to try to treat sickle cell for the first time. She jumped at the chance to volunteer.

"I was excited," Gray says.

CRISPR enables scientists to edit genes much more easily than ever before. Doctors hope it will give them a powerful new way to fight cancer, AIDS, heart disease and a long list of genetic afflictions.

"CRISPR technology has a lot of potential use in the future," Frangoul says.

To try to treat Gray's sickle cell, doctors started by removing bone marrow cells from her blood last spring.

Next, scientists used CRISPR to edit a gene in the cells to turn on the production of fetal hemoglobin. It's a protein that fetuses make in the womb to get oxygen from their mothers' blood.

"Once a baby is born, a switch will flip on. It's a gene that tells the ... bone marrow cells that produce red cells to stop making fetal hemoglobin," says Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's TriStar Centennial Medical Center.

The hope is that restoring production of fetal hemoglobin will compensate for the defective adult-hemoglobin sickle cells that patients produce.

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain. Ed Reschke/Getty Images hide caption

Patients with sickle cell disease have blood cells that are stiff and misshapen. The cells don't carry oxygen as well and clog up the bloodstream, resulting in periodic bouts of excruciating pain.

"We are trying to introduce enough ... fetal hemoglobin into the red blood cell to make the red blood cell go back to being happy and squishy and not sticky and hard, so it can go deliver oxygen where it's supposed to," Frangoul says.

Then on July 2, after extracting Gray's cells and sending them to a lab to get edited, Frangoul infused more than 2 billion of the edited cells into her body.

"They had the cells in a big syringe. And when it went in, my heart rate shot up real high. And it kind of made it hard to breath," Gray says. "So that was a little scary, tough moment for me."

After that moment passed, Gray says, she cried. But her tears were "happy tears," she adds.

"It was amazing and just kind of overwhelming," she says, "after all that I had went through, to finally get what I came for."

The cells won't cure sickle cell. But the hope is that the fetal hemoglobin will prevent many of the disease's complications.

"This opens the door for many patients to potentially be treated and to have their disease modified to become mild," Frangoul says.

The procedure was not easy. It involved going through many of the same steps as a standard bone marrow transplant, including getting chemotherapy to make room in the bone marrow for the gene-edited cells. The chemotherapy left Gray weak and struggling with complications, including painful mouth sores that made it difficult to eat and drink.

But Gray says the ordeal will have been worth it if the treatment works.

She calls her new gene-edited cells her "supercells."

"They gotta be super to do great things in my body and to help me be better and help me have more time with my kids and my family," she says.

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer. Meredith Rizzo/NPR hide caption

Gray was diagnosed with sickle cell disease as an infant. She was considering a bone marrow transplant when she heard about the CRISPR study and jumped at the chance to volunteer.

Concerns about risk

Other doctors and scientists are excited about the research. But they're cautious too.

"This is an exciting moment in medicine," says Laurie Zoloth, a bioethicist at the University of Chicago. "Everyone agrees with that. CRISPR promises the capacity to alter the human genome and to begin to directly address genetic diseases."

Still, Zoloth worries that the latest wave of genetic studies, including the CRISPR sickle cell study, may not have gotten enough scrutiny by objective experts.

"This a brand-new technology. It seems to work really well in animals and really well in culture dishes," she says. "It's completely unknown how it works in actual human beings. So there are a lot of unknowns. It might make you sicker."

Zoloth is especially concerned because the research involves African Americans, who have been mistreated in past medical studies.

Frangoul acknowledges that there are risks with experimental treatments. But he says the research is going very slowly with close oversight by the Food and Drug Administration and others.

"We are very cautious about how we do this trial in a very systematic way to monitor the patients carefully for any complications related to the therapy," Frangoul says.

Gray says she understands the risks of being the first patient and that the study could be just a first step that benefits only other patients, years from now. But she can't help but hope it works for her.

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville. Meredith Rizzo/NPR hide caption

Dr. Haydar Frangoul, medical director of pediatric hematology/oncology at HCA Healthcare's Sarah Cannon Research Institute and TriStar Centennial Medical Center, is leading the study in Nashville.

She imagines a day when she may "wake up and not be in pain" and "be tired because I've done something not just tired for no reason." Perhaps she could play more with her kids, she says, and look forward to watching them grow up.

"That means the world to me," Gray says.

It could be many weeks or even months before the first clues emerge about whether the edited cells are safe and might be working.

"This gives me hope if it gives me nothing else," she says in July.

Heading home at last

About two months later, Gray has recovered enough to leave the hospital. She has been living in a nearby apartment for several weeks.

Enough time has passed since Gray received the cells for any concerns about immediate side effects from the cells to have largely passed. And her gene-edited cells have started working well enough for her immune system to have resumed functioning.

So Gray is packing. She will finally go home to see her children in Mississippi for the first time in months. Gray's husband is there to drive her home.

"I'm excited," she says. "I know it's going to be emotional for me. I miss the hugs and the kisses and just everything."

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss. Meredith Rizzo/NPR hide caption

After living for months in Nashville, where the study was taking place, Gray packs her bags to finally go home to her kids and family in Forest, Miss.

Gray is wearing bright red glittery eye shadow. It matches her red tank top, which repeats "I am important" across the front.

She unzips a suitcase and starts pulling clothes from the closet.

"My goodness. Did I really bring all this?" she says with a laugh.

Before Gray can finish packing and depart, she has to stop by the hospital again.

"Are you excited about seeing the kids?" Frangoul says as he greets her. "Are they going to have a big welcome sign for you in Mississippi?"

Turns out that Gray has decided to make her homecoming a surprise.

"I'm just going to show up tomorrow. Like, 'Mama's home,' " she says, and laughs.

After examining Gray, Frangoul tells her that she will need to come back to Nashville once a month for checkups and blood tests to see if her genetically modified cells are producing fetal hemoglobin and giving her healthier red blood cells.

"We are very hopeful that this will work for Victoria, but we don't know that yet," Frangoul says.

Gray will also keep detailed diaries about her health, including how much pain she's experiencing, how much pain medication she needs and whether she needs any blood transfusions.

"Victoria is a pioneer in this. And we are very excited. This is a big moment for Victoria and for this pivotal trial," Frangoul says. "If we can show that this therapy is safe and effective, it can potentially change the lives of many patients."

Gray hopes so too.

Excerpt from:

Sickle Cell Therapy With CRISPR Gene Editing Shows Promise : Shots - Health News - NPR

CAMBRIDGE, Mass., Dec. 23, 2019 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced that Sarepta and Roche have entered into a licensing agreement providing Roche exclusive commercial rights to SRP-9001 (AAVrh74.MHCK7.micro-dystrophin), Sareptas investigational gene therapy for Duchenne muscular dystrophy (DMD), outside the United States. Under the agreement, Sarepta will receive $1.15 billion in an upfront payment and an equity investment; up to $1.7 billion in regulatory and sales milestones; and royalties on net sales, anticipated to be in the mid-teens. In addition, Roche and Sarepta will equally share global development expenses. Sarepta retains all rights to SRP-9001 in the United States.

The collaboration combines Sareptas leading gene therapy candidate for DMD with Roches global reach, commercial presence and regulatory expertise to accelerate access to SRP-9001 for patients outside the United States. DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. SRP-9001, currently in clinical development for DMD, is designed to deliver the micro-dystrophin-encoding gene directly to the muscle tissue for the targeted production of the micro-dystrophin protein.

As a mission-driven organization, we are inspired to partner with Roche with the goal of bringing SRP-9001 to patients outside the United States. This collaboration will not only increase the speed with which SRP-9001 could benefit DMD patients outside the United States, but will also greatly expand the scope of territories within which we could potentially launch SRP-9001 and improve and save lives, said Doug Ingram, president and chief executive officer, Sarepta. In addition to the validation that comes from joining forces with Roche, this licensing agreement one of the most significant ex-U.S. licensing transactions in biopharma will provide Sarepta with the resources and focus to accelerate our gene therapy engine and, if successful, bring SRP-9001 to patients as quickly as possible, potentially transforming the lives of countless DMD patients across the globe.

Said James Sabry, Head of Roche Pharma Partnering, We are excited to enter this licensing agreement with Sarepta. By working together to provide SRP-9001 to patients, we hope to fundamentally transform the lives of patients and families living with this devastating disorder for which there are currently only limited treatment options.

As part of the agreement, Sarepta will continue to be responsible for the global development plan and manufacturing build out for SRP-9001. Through its leading hybrid manufacturing platform, Sarepta will remain responsible for manufacturing of clinical and commercial supplies. Sarepta has also granted Roche an option to acquire ex-U.S. rights to certain future DMD-specific programs, in exchange for separate milestone and royalty considerations, and cost sharing.

The closing of the transaction is subject to the expiration or termination of the waiting period under the Hart-Scott-Rodino Antitrust Improvements Act of 1976 and other customary conditions. The parties anticipate that the agreement will close in the first quarter of 2020.

Goldman Sachs & Co. LLC is acting as the lead financial advisor to Sarepta. Morgan Stanley & Co. LLC is also serving as a financial advisor and Ropes & Gray LLP is serving as legal advisor to Sarepta.

Conference Call InformationThe conference call may be accessed by dialing (844) 534-7313 for domestic callers and (574) 990-1451 for international callers. The passcode for the call is 2077714. Please specify to the operator that you would like to join the "Sarepta Therapeutics Conference Call." The conference call will be webcast live under the investor relations section of Sarepta's website at http://www.sarepta.com and will be archived there following the call for 90 days. Please connect to Sarepta's website several minutes prior to the start of the broadcast to ensure adequate time for any software download that may be necessary.

About Sarepta TherapeuticsSarepta is at the forefront of precision genetic medicine, having built an impressive and competitive position in Duchenne muscular dystrophy (DMD) and more recently in gene therapies for limb-girdle muscular dystrophy diseases (LGMD), Charcot-Marie-Tooth (CMT), MPS IIIA and other CNS-related disorders, totaling over 20 therapies in various stages of development. The Companys programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. Sarepta is fueled by an audacious but important mission: to profoundly improve and extend the lives of patients with rare genetic-based diseases. For more information, please visit http://www.sarepta.com.

Sarepta Forward-Looking StatementThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include but are not limited to statements regarding the closing of the transaction; Sareptas right to receive any upfront payment or equity investment from Roche pursuant to the agreement; Sareptas right to receive regulatory and sales milestones, and royalty payments from Roche pursuant to the agreement; Roches obligation to share global development expenses pursuant to the agreement; the continued development and manufacturing of SRP-9001; SRP-9001 expected delivery of micro-dystrophin-encoding gene directly to the muscle tissue and the expected production of the micro-dystrophin protein; the expected increased speed with which SRP-9001 could benefit patients outside the United States and expansion of territories within which Sarepta could launch SRP-9001; the expectation that the licensing agreement will provide Sarepta with the resources and focus to accelerate its gene therapy engine and potentially bringing SRP-9001 to patients as quickly as possible and transforming the lives of countless DMD patients across the globe; potential regulatory approvals of SRP-9001; and the potential launch and commercialization of SRP-9001.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Known risk factors include, among others, market conditions, the expected benefits and opportunities related to the licensing agreement may not be realized or may take longer to realize than expected due to a variety of reasons, including any inability of the parties to perform their commitments and obligations under the agreement, challenges and uncertainties inherent in product research and development and manufacturing limitations; success in preclinical testing and early clinical trials, especially if based on a small patient sample, does not ensure that later clinical trials will be successful, and early results from a clinical trial do not necessarily predict final results; our data for SRP-9001 may not be sufficient for obtaining regulatory approval; Sarepta may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing SRP-9001 to market, for various reasons, some of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, and regulatory, court or agency decisions; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2018 and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review.

Any of the foregoing risks could materially and adversely affect the Companys business, results of operations and the trading price of Sareptas common stock. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. Sarepta does not undertake any obligation to publicly update its forward-looking statements based on events or circumstances after the date hereof.

Internet Posting of Information

We routinely post information that may be important to investors in the 'For Investors' section of our website at http://www.sarepta.com. We encourage investors and potential investors to consult our website regularly for important information about us.

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

Investors:Ian Estepan, 617-274-4052iestepan@sarepta.com

Media:Tracy Sorrentino, 617-301-8566tsorrentino@sarepta.com

See original here:

Sarepta Therapeutics Announces Partnership with Roche in Territories Outside the United States for its Investigational Micro-dystrophin Gene Therapy...

Corrections & Clarifications: An earlier version of this story incorrectly reported Edward Aschoff's cause of death, which has yet to be officially determined.

ESPN college football reporter Edward Aschofftweeted about battling multifocal pneumonia before his deathTuesday, his 34th birthday, drawing widespread attention to the disease.

On Thursday,Katy Berteau, Aschoff's fiance, revealed that battlepreceded a later presumed diagnosis.

"Edward was admitted to the hospital a week after our first visit to the ER, where he was diagnosed with multifocal pneumonia,"Berteau tweeted fromAschoff's Twitter account.

"After failed antibiotic treatment, with worsening of symptoms, we took him back to the ER and he was immediately admitted.

"After many tests - bone marrow and lung biopsies - treatment was started for a presumed diagnosis of HLH, an unregulated, over-activation of the immune system that causes it to attack itself and other healthy tissues,"Berteau tweeted.

"Within 3 days of being moved into the ICU, he passed."

Aschoff first tweeted about his condition on Dec. 5 asking his followers, Anyone ever had multifocal (bilateral) pneumonia in their early 30s as some who never gets sick and has a very good immune system?

He then replied to another tweet the same day, detailing the symptoms he had been dealing with for weeks: So I had a virus for two weeks. Fever and cough and the doctors think it turns into this multifocal pneumonia recently. Im on day 4 of antibiotics. Days are getting better but nights are basically fever and coughing and sweating.

Here's more information about the illnessAschoff tweeted about before his death:

Dr. Marc Sala, assistant professor of medicine inpulmonary critical care at Northwestern University says pneumonia is an infection of the lungs' air sacs, or tissue."Multifocal" pneumonia means that the infectionis not just affecting one partof the lung but multiple sections.

"Bilateral" means that the infection is present in both lungs.

Sala says that the more tissue infected, the more severe the pneumonia.

Pneumonia is contagious. But Sala says not much is known in the medical community about how peopleget pneumonia.

"What makes one person develop pneumonia versus another is still a developing science because it has a lot to do with the individual person," he says.

Certain characteristics such as genetic factors, a patient's immune system, medical history and age can determine whether a person is infected.

'Brighton ax murder': Decades after his daughters death by ax in 1982, a father waits for justice

Nurses who kill: Medical murderers and the mystery of the Clarksburg VA hospital in West Virginia

The common cold is one of the most well-known and established risk factors of developing pneumonia,Sala says.

"Other viruses(such as the flu) can predispose you to a compromised immune system of the lungs," he says.

Although pneumonia isn't predictable, Sala says, the best way to mitigate other viruses that could develop into pneumonia is to practice good hand hygiene, avoid people who may be sick and get the flu shot every year.

'Men should get engagement rings too': Lindsey Vonn proposes to P.K. Subban

10 lists that define the 2010s: Warming temperatures, growing cities, TIME people of the year

According to the Mayo Clinic, pneumonia symptoms can vary from mild to severe depending on the cause of infection, age and the patient's overall health.

Milder symptoms look similar to a cold or flu and can include chest pain when breathing or coughing, fatigue, fever accompanied by sweating and shaking chills, nausea, vomiting or diarrhea and shortness of breath.

Sala says that the only way to confirm a diagnosis of pneumonia is to visit a doctor to get an x-ray and physical exam.

"If symptoms arent improving with just conservative measures at home ... in the time course of several days and youre getting worse that should prompt an evaluation."

Contributing: Ellen J. Horrow, USA TODAY.

Follow Adrianna Rodriguez on Twitter: @AdriannaUSAT.

Autoplay

Show Thumbnails

Show Captions

Read or Share this story: https://www.usatoday.com/story/news/health/2019/12/26/espn-edward-aschoff-34-dies-multifocal-pneumonia-what-it/2746436001/

More here:

What is multifocal pneumonia, the illness ESPN reporter Edward Aschoff tweeted about before his death? - USA TODAY

From the cradle to the grave

There is evidence to suggest that the unique microbiome of each person starts to take shape even while we are still growing in the womb. From birth and throughout life, it continues to develop and evolve, influenced by genetics, as well as environmental factors such as diet, nutrition and exposure to drugs such as antibiotics.

It is estimated that an average adult carries about two kilograms worth of microbes in their gut. In fact, the number of these organisms often outnumber our own cells. Most of the time, we may be carrying more microbial genes than human genes in our bodies. The latter aid in digestion and help produce essential vitamins (such as vitamins B and K) and maintain a healthy gut by preventing overgrowth and invasion by disease-causing microbes. But increasingly, research is finding that there is more to our microbiomes than just promoting gut health: It can impact weight, immunity, mood, behaviour, energy and overall wellness.

Some experts claim that up to 90 percent of diseases can be traced back in some way to the gut and the health of the microbiome. The gut microbiome, and its diversity, has been shown to influence many conditions not traditionally considered microbe related from whether a person develops obesity, heart disease, asthma or diabetes, to neurological conditions such as Parkinsons disease and dementia, to development of cancer, right down to how well we respond to chemotherapy and vaccines.

A new frontier

Microbiome research is an exploding field of science growing at an exponential rate. New knowledge is being added almost daily. The organisms being discovered have names not found in textbooks, being unknowable to us a mere few years ago. Unlike their disease-causing counterparts, they live symbiotically within the host and are not found in clinical specimens. But advances in genetic analysis technology have propelled the exploration of this new frontier of science.

Researchers have now identified more than 10,000 species of microbes living in and on the human body. The next challenge is to tease out and define the apparent associations between the microbiome, health and disease and develop ways to manipulate it to improve health, as we have done with antibiotics and probiotics.

The more diverse, the better

It remains to be defined how exactly the microbiome exerts its health consequences on the host or what makes a healthy microbiome. Experts agree that diversity is a good thing when it comes to gut microbes. The diversity of the travellers we carry appears instrumental in the development of a robust immune system. Association with disease is usually observed when this diversity is reduced or lost. Diet is a major influence on this diversity by dictating the environment in which certain microbes can take up long-term residence within the gut. For example, diets high in saturated fats, which are linked to conditions such as diabetes and heart disease,are also thought to reduce microbial diversity.

How you can influence your microbiome

Here are a few tips to cultivate as much diversity as possible in your gut microbiome:

Increase your fibre intake

Dietary fibre usually comes from plant-based food ingredients that are not broken down by enzymes in the gastrointestinal tract. Most adults should aim to have 25 35 grams of fibre in their diet every day. Fibre supports the growth and diversity of the microbiome and has the added benefits of lowering your risk of heart disease, diabetes and colon cancer.

Eat a wide and seasonal range of fruits, nuts and vegetables

The variety and the types of fibres found within different fruits and vegetables are thought to support different microbial species, thereby contributing to the overall diversity.

Include fermented foods in your diet

Fermented foods such as pickled vegetables, staples of the Burmese dinner tables everywhere, have been shown to be beneficial in improving the diversity of the microbiome and gut function. Other fermented foods include yoghurt, kimchi, soybean-based products such as soy sauce and tempeh.

Avoid artificial sweeteners.

Artificial sweeteners such as saccharin, sucralose or aspartame may be sold as sugar substitutes or are found in sugar-free beverages. These are marketed as a healthier no-calorie alternative to natural sugars, but they have been shown to disrupt the gut microbiome.

Avoid antibiotics and non-essential medicines

Antibiotics may be life-saving when taken for the right reasons. But taken unnecessarily, they indiscriminately wipe out many beneficial microbes, reducing the diversity of the microbiome with effects lasting up to years. Dangerous and pathogenic bacteria may flourish in absence of the microbiome diversity which may result in serious illness. Even non-antibiotic medications may alter gut microbiome by altering the colonic environment so best to play it safe and only take them when necessary.

Dr Thel Khin Hla is a doctor with the Myanmar Oxford Clinical Research Unit in Yangon.

Continue reading here:

The travellers within us - Myanmar Times

As the old saying goes, strike when the iron is hot. That's what a new gene editing start-up named Beam Therapeutics hopes to do by conducting an initial public offering (IPO) less than two years after forming and more than a year before it asks regulators for permission to begin clinical trials. Given the excitement over genetic medicines, it might be wise to take advantage of the open window now.

Assuming the IPO proceeds as planned, Beam Therapeutics will offer investors a second chance to own a next-generation gene editing technology platform and the first next-generation CRISPR tool. Here's why investors might want to keep the business on their radar.

Image source: Getty Images.

Beam Therapeutics bears some similarities to Editas Medicine (NASDAQ:EDIT). Both trace their origins back to the Broad Institute in Boston. They share a trio of all-star scientific founders: Dr. Feng Zhang, Dr. David Liu, and Dr. Keith Joung. Each company's technology platform is built on CRISPR-based tools.

But the differences are more important for investors. Editas Medicine is developing gene editing tools that require Cas enzymes to cut both strands of DNA. While that theoretically provides the ability to delete or insert genetic sequences to treat diseases, the approach relies on innate DNA repair mechanisms. When the built-in safeguards on those mechanisms break down, cells can turn cancerous. CRISPR-CasX tools can also create unintended genetic edits, and have a relatively low efficiency.

Beam Therapeutics is developing gene editing tools based on a new technique called base editing. The enzymatic approach doesn't make double-stranded breaks in DNA. Instead, it induces chemical reactions to change the sequence of the genetic alphabet -- A (adenine), T (thymine), C (cytosine), and G (guanine) -- one letter at a time. Base editing can make A-to-G edits, C-to-T edits, G-to-A edits, and T-to-C edits.

The next-generation approach decouples CRISPR gene editing tools and the need to make double-stranded breaks in DNA, which is the most pressing concern facing Editas Medicine, CRISPR Therapeutics (NASDAQ:CRSP), and Intellia Therapeutics (NASDAQ:NTLA).

Clinical Consideration

CRISPR-CasX Gene Editing

CRISPR Base Editing

Does it cut DNA?

Yes, enzymatically cuts both strands of DNA

No

Can be used to insert new genetic material into a sequence?

Yes

No, but it can enzymatically change an existing DNA sequence

Does it trigger DNA repair mechanisms?

Yes

No

Source: Beam Therapeutics, author.

While base editing can't make every possible edit (example: A-to-T edits), it can target a number of disease-driving genetic errors. And Beam Therapeutics has inked important collaboration deals to augment the capabilities of its technology platform:

After reviewing the details, investors see that there's a tangled web of related transactions that all flow back to the Broad Institute, which is going to great lengths to extract every ounce of value from its scientific discoveries. Similar actions have caused a stir in the scientific community in recent years. If the profit-seeking terms of the non-profit research institution's agreements are too strict, then it may pose a risk to Beam Therapeutics at the expense of investors.

Image source: Getty Images.

Investors familiar with gene editing stocks will immediately recognize the programs included in the pipeline of the base editing pioneer. The lead assets take aim at blood disorders, and are part of a push to engineer better immunotherapies to treat cancer.

In beta thalassemia and sickle cell disease, Beam Therapeutics is first attempting to increase the production of fetal hemoglobin, which confers natural immunity to both conditions. That's similar to the lead drug candidate of CRISPR Therapeutics, which recently demonstrated promising results from the first two patients in a phase 1 clinical trial.

A second program in sickle cell disease aims to directly correct the genetic mutation responsible for the blood disorder. It involves changing a single base -- perfectly suited for base editing.

In immunotherapy, Beam Therapeutics is working to engineer better chimeric antigen receptor T (CAR-T) cells that can be used as cellular medicines to treat various types of cancers. CRISPR Therapeutics, Editas Medicine, and Intellia Therapeutics are deploying CRISPR gene editing in the same applications, while Precision BioSciences (NASDAQ:DTIL) is leaning on ARCUS gene editing to do the same. The latter's lead drug candidates are in immunotherapy, a unique distinction among gene editing stocks.

Beam Therapeutics' pipeline also includes a range of potential assets aimed at gene correction, gene silencing, and more complex editing, but none have entered clinical trials. The company doesn't expect to file investigational new drug (IND) applications -- required for regulators to sign off on the start of clinical trials -- until 2021. But since the window for an IPO might be slammed shut by then, the business is exploring a market debut now.

There aren't many details in the company's S1 filing concerning a potential date for a market debut or how much money the company is aiming to raise. The filing says $100 million, but that's just a placeholder for the initial submission. The actual amount will be determined once Wall Street gets an idea of the level of interest in an IPO, which will determine the number of shares to offer and the price.

Assuming the IPO takes place, Beam Therapeutics and base editing offer investors a technological upgrade over the first-generation gene editing platforms leaning on CRISPR-CasX tools. The next-generation tools aren't perfect, and there are risks related to the agreements with the Broad Institute and sister start-ups, but this is certainly a gene editing stock worth watching.

Read the original here:

This Start-up Might Be the Next Gene Editing IPO - The Motley Fool

Are you one of the 26 million people who have experienced genetic testing by companies such as 23andMe or Ancestry? These companies promise to reveal what your genes say about your health and ancestry. Genes are, indeed, the instruction book containing the code that makes you a unique human being. This specific code which you inherit from your parents is what makes you, you.

The genetic coding system works amazingly well, but like all systems, occasionally things dont go as planned. You may inherit a gene that increases your chance of developing a health condition and sometimes the code develops an error causing you to have a devastating disease.

If genetic testing is so powerful in analysing and understanding your health, why cant you just as easily have this same genetic information inform your care at the doctors office? To answer this question, lets first look at the field of using genetic information to drive your healthcare (often referred to as precision or personalized medicine).

Across the globe, researchers devote enormous amounts of time and effort to understand how human genes impact health and billions of dollars are invested. The knowledge of what impact specific genes have on our health has increased tremendously and continues to do so at an amazing pace. Our increased understanding of genes, and how they affect our health, is driving novel methods to halt diseases and new ways of thinking about how medications can be developed to treat diseases.

Precision medicine is a growth area

With all this money and effort being expended, why isnt the use of your genetic information a standard part of your medical care? As the Kaiser Permanente Fellow to the World Economic Forums Precision Medicine Team, I recently had the opportunity to interview leaders from every aspect of Precision Medicine to understand the barriers preventing genetic testing from becoming a standard part of your healthcare.

Those with whom I spoke included insurance companies who pay for the tests, doctors who use and interpret them, genetic counsellors who help you understand test results, diagnostic companies which develop testing, government healthcare regulators, researchers making astonishing discoveries and healthcare organizations who are determining how best to deploy genetic testing.

These interviews suggest that the science behind genetic testing and the knowledge of how genes impact health is far ahead of our ability to make full use of this information in healthcare. Moving genetic testing into your doctors office requires a complex set of technologies, processes, knowledge and payments. Though many of the barriers inhibiting this movement were unique and complex, there were some consistent and common themes:

1. The limited expertise in genetics within healthcare systems. The need for education of healthcare providers as well as the public was regularly highlighted. The use of genetics in healthcare requires specialized knowledge that is outside the expertise of most doctors. Healthcare providers simply dont have time to study this new and rapidly changing information as their hands are full just keeping up with the latest trends and findings in their specialities. Additionally, education on genetics in healthcare is needed for the public. As one person interviewed said: The public watches CSI and thinks the use of DNA and genetics is black and white; using genetics in healthcare is rarely black and white

2. The lack of sufficient genetic counsellors. Genetic counsellors are often used to engage patients prior to testing and after results have been received, providing them with the detailed and nuanced information required for many of these tests. They also support doctors when they need assistance in making decisions about genetic testing and understanding the test results.

3. To successfully embed genetics into your care, doctors need the workflows for genetic testing (receiving results and understanding the impact on their care plans) to become a seamless part of their work. Clinical decision support software for genetics should alert the healthcare provider when genetic testing is merited with a patient, based on information the provider has entered during their examination. The software should then provide a list of appropriate tests and an explanation of why one might be used over another. After doctors order the test, they believe is most appropriate, the system should inform them of the results in clear, easily understandable language. The results should inform the doctor if the care plan for this patient should be modified (with suggestions for how the care should change).

4. Coverage of payments for genetic testing. If such tests are not paid for by insurers or government healthcare agencies (the payers), doctors simply wont order them. In the US and many other countries, there is patchwork coverage for genetic testing. Some tests are covered under specific circumstances, but many are not covered at all. The major reason cited by the payers for not covering genetic testing is a lack of evidence of clinical efficacy. In other words, do these tests provide actionable information, that your doctor can use to ensure better health outcomes? Until the payers see sufficient evidence of clinical efficacy, they will be hesitant to pay for many types of genetic testing. Doctors are concerned about the same thing, according to my research. They want to see the use of these tests in large populations, so they can determine that there is a benefit to using them.

Using your genetic information in healthcare is much more complex than taking a direct-to-consumer genetic test such as those offered by 23andMe. Healthcare is a multifaceted system and doctors already have too much on their plate. As such, there must be sufficient proof that the use of genetic testing will result in better health outcomes for the populations these clinicians serve before it's introduced into this setting.

We cannot hesitate in the face of the above complexities. As I completed the interviews which revealed these barriers, I stumbled across a journal article on this very subject. Written by a prominent group of doctors and researchers from government and leading universities in 2013, it highlights these same barriers and that virtually no progress has been made in the ensuing seven years. This is why I am focusing my fellowship at the World Economic Forum on a new project called Moving Genomics to the Clinic. Taking advantage of the multistakeholder platform of the Forum, the project will quicken the pace of tackling these barriers so that the use of genetic information can become a standard part of your healthcare experience.

License and Republishing

World Economic Forum articles may be republished in accordance with our Terms of Use.

Written by

Arthur Hermann, Fellow, Precision Medicine, World Economic Forum

The views expressed in this article are those of the author alone and not the World Economic Forum.

Read the original post:

How to bring precision medicine into the doctor's office - World Economic Forum