StemCell Therapy

This article is part of the Technology Insight series, made possible with funding from Intel.

When my son was a toddler, he went to his pediatrician for a routine CAT scan. Easy stuff. Just a little shot to subdue him for a few minutes. Hed be awake and finished in a jiffy.

Except my son didnt wake up. He lay there on the clinic table, unresponsive, his vitals slowly falling. The clinic had no ability to diagnose his condition. Five minutes later, he was in the back of an ambulance. My wife and I were powerless to do anything but look on, frantic with worry for our boys life.

It turned out that hed had a bad reaction to a common hydrochloride sedative. Once that was figured out, doctors quickly brought him back around, and he was fine.

But what if, through groundbreaking mixtures of compute, database, and AI technologies, a quick round of analyses on his blood and genome could have revealed his potential for such a reaction before it became a critical issue?

What if it were possible to devise a course of treatment specific to him and his bodys unique conditions, rather than accepting a cookie-cutter approach and dealing with the ill effects immediately after?

And what if that could be done with small, even portable medical devices equipped with high-bandwidth connectivity to larger resources?

In short, what if, through the power of superior computing and next-generation wireless connectivity, millions of people like my son could be quickly, accurately treated on-site rather than endure the cost and trauma of legacy medical methods?

These questions I asked about my son are at the heart of todays efforts in precision medicine. Its the practice of crafting treatments tailored to individuals based on their characteristics. Precision medicine spans an increasing number of fields, including oncology, immunology, psychiatry, and respiratory disorders, and its back end is filled with big data analytics.

Key Points:

Pairing drugs to gene characteristics only covers a fraction of the types of data that can be pooled to target specific patient care.

Consider the Montefiore Health System in the Bronx. It has deployed a semantic data lake, an architecture for collecting large, disparate volumes of data and collating them into usable forms with the help of AI. Besides the wide range of data specific to patients collected onsite (including from a host of medical sensors and devices), Montefiore healthcare professionals also collate data from sources as needed, including PharmGKB databank (genetic variations and drug responses), the National Institute of Healths Unified Medical Language System (UMLS), and the Online Mendelian Inheritance in Man (human genomic data).

Long story short, the Intel/Cloudera/Franz-based solution proved able to accurately create risk scores for patients, predict whether they would have a critical respiratory event, and advise doctors on what actions to take.

We are using information for the most critically ill patients in the institution to try and identify those at risk of developing respiratory failure (so) we can change the trajectory, noted Dr. Andrew Racine, Montefiores system SVP and chief medical officer.

Now that institutions like Montefiore can perform AI-driven analytics across many databases, the next step may be to integrate off-site communications via 5G networking. Doing so will enable physicians to contribute data from the field, from emergency sites to routine in-home visits, and receive real-time advice on how to proceed. Not only can this enable healthcare professionals to deliver faster, more accurate diagnoses, it may permit general physicians to offer specialized advice tailored to a specific patients individual needs. Enabling caregivers like this with guidance from afar is critical in a world that, researchers say, faces a shortage 15 million healthcare workers by 2030.

Enabling services like these is not trivial in any way. Consider the millions of people who might need to be genetically sequenced in order to arrive at a broad enough sample population for such diagnostics. Thats only the beginning. Different databases must be combined, often over immense distances via the cloud, without sacrificing patients rights or privacy. Despite the clear need for this, according to the Wall Street Journal, only 4% of U.S. cancer patients in clinical trials have their genomic data made available for research, leaving most treatment outcomes unknown to the research and diagnostic communities. New methods of preserving patient anonymity and data security across systems and databases should go a long way toward remedying this.

One promising example: using the processing efficiencies of Intel Xeon platforms in handling the transparent data encryption (TDE) of Epic EHR patient information with Oracle Database. Advocates say the more encryption and trusted execution technologies, such as SGX, can be integrated from medical edge devices to core data centers, the more the public will learn to allow its data to be collected and used.

Beyond security, precision medicine demands exceptional compute power. Molecular modeling and simulations must be run to assess how a drug interacts with particular patient groups, and then perhaps run again to see how that drug performs the same actions in the presence of other drugs. Such testing is why it can take billions of dollars and over a decade to bring a single drug to market.

Fortunately, many groups are employing new technologies to radically accelerate this process. Artificial intelligence plays a key role in accelerating and improving the repetitive, rote operations involved in many healthcare and life sciences tasks.

Pharmaceuticals titan Novartis, for example, uses deep neural network (DNN) technology to accelerate high-content screening, which is the analysis of cellular-level images to determine how they would react when exposed to varying genetic or chemical interactions. By updating the processing platform to the latest Xeon generation, parallelizing the workload, and using tools like the Intel Data Analytics Acceleration Library (DAAL) and Intel Caffe, Novartis realized nearly a 22x performance improvement compared to the prior configuration. These are the sorts of benefits healthcare organizations can expect from updating legacy processes with platforms optimized for acceleration through AI and high levels of parallelization.

Interestingly, such order-of-magnitude leaps in capability, while essential for taming the torrents of data flowing into medical databases, can also be applied to medical IoT devices. Think about X-ray machines. Theyre basically cameras that require human specialists (radiologists) to review images and look for patterns of health or malady before passing findings to doctors. According to GE Healthcare, hospitals now generate 50 petabytes of data annually. A staggering 90% comes from medical imaging, GE says, with more than 97% unanalyzed or unused. Beyond working to use AI to help reduce the massive volume of reject images, and thus cut reduce on multiple fronts, GE Healthcare teamed with Intel to create an X-ray system able to capture images and detect a collapsed lung (pneumothorax) within seconds.

Simply being able to detect pneumothorax incidents with AI represents a huge leap. However, part of the projects objective was to deliver accurate results more quickly and so help to automate part of the diagnostic workload jamming up so many radiology departments. Intel helped to integrate its OpenVINO toolkit, which enables development of applications that emulate human vision and visual pattern recognition. Those workloads can then be adapted for processing across CPUs, GPU, AI-specific accelerators and other processors.

With the optimization, the GE X-ray system performed inferences (image assessments) 3.3x faster than without. Completion time was less than one second per image dramatically faster than highly trained radiologists. And, as shown in the image above, GEs Optima XR240amx X-ray system is portable. So this IoT device can deliver results from a wide range of places and send results directly to doctors devices in real time over fast connections, such as 5G. A future version could feed analyzed X-rays straight into patient records. There, they become another factor in the multivariate pool that constitutes the patients dataset, which in turn, enables personalized recommendations by doctors.

By now, you see the problem/solution pattern:

The U.S. provides a solid illustration of the impact of population in this progression. According to the U.S. Centers for Disease Control (CDC), even though the rate of new cancer incidents has flattened in the last several years, the countrys rising population pushed the number of new cases diagnosed from 1.5 million in 2010 to 1.9 million in 2020, driven in part by rising rates in overweight, obesity, and infections.

The white paper Accelerating Clinical Genomics to Transform Cancer Care (below) paints a stark picture of the durations involved in traditional approaches to handling new cancer cases from initial patient visit to data-driven treatment.

At each step, delays plague the process extending patient anxiety, increasing pain, even leading to unnecessary death.

Intel created an initiative called All in One Day to create a goal for the medical industry: take a patient from initial scan(s) to precision medicine-based actions for remediation in only 24 hours. This includes genetic sequencing, analysis that yields insights into the cellular- and molecular-level pathways involved in the cancer, and identification of gene-targeted drugs able to deliver the safest, most effective remedy possible.

To make All in One Day possible, the industry will require secure, broadly trusted methods for regularly exchanging petabytes of data. (Intel notes that a typical genetic sequence creates roughly 1TB of data. Now, multiply that across the thousands of genome sequences involved in many genomic analysis operations.) The crunching of these giant data sets calls for AI and computational horsepower beyond what todays massively parallel accelerators can do. But the performance is coming.

As doctors will have to service ever-larger patient populations, expect them to need data results and visualizations delivered to wherever they may be, including in forms animated or rendered in virtual reality. This will require 5G-type wireless connectivity to facilitate sufficient data bandwidth to whatever medical IoT devices are being used.

If successful, more people will get more personalized help and relief than ever possible. The medical IoT and 5G dovetail with other trends now reshaping modern medicine and making these visions everyday reality. A 2018 Intel survey showed that 37% of healthcare industry respondents already use AI; the number should rise to 54% by 2023. Promising new products and approaches appear daily. A few recent examples are here, here and here.

As AI adoption continues and pairs with faster hardware, more diverse medical devices, and faster connectivity, perhaps we will soon reach a time when no parent ever has to watch an unresponsive child whisked away by ambulance because of adverse reactions that might have been avoided through precision medicine and next-gen technology.

Read more here:
AI, 5G, and IoT can help deliver the promise of precision medicine - VentureBeat

WALTHAM, Mass.--(BUSINESS WIRE)--Dyne Therapeutics, a biotechnology company pioneering targeted therapies for patients with serious muscle diseases, today announced the addition of three key members to its leadership team: Oxana Beskrovnaya, Ph.D., senior vice president and head of research; Chris Mix, M.D., senior vice president, clinical development; and John Najim, vice president, chemistry, manufacturing and controls (CMC).

Dyne is establishing a leadership position in muscle disease therapeutics by combining transformative science with an organizational passion for changing the lives of patients, said Joshua Brumm, president and chief executive officer of Dyne. We are thrilled to welcome Oxana, Chris and John to our growing team. Leveraging their collective experience in the discovery and development of novel medicines, we are poised to rapidly advance our programs toward the clinic and are fully focused on execution.

Dr. Beskrovnaya is an accomplished R&D leader with a strong track record of discovering and developing first-in-class therapeutics for rare genetic diseases. Prior to joining Dyne, she served as head of musculoskeletal and renal research in Sanofis rare disease and neurological unit, where she advanced a pipeline of drug candidates using multiple therapeutic modalities, including nucleic acids, proteins and small molecules. Dr. Beskrovnaya is the author of numerous patents, invited reviews, editorials, book chapters and original research articles in major scientific journals. She received her Ph.D. in genetics from Moscow Genetics Institute, followed by postdoctoral fellowship training in neuromuscular diseases at the Howard Hughes Medical Institute at the University of Iowa.

Dr. Mix brings extensive clinical development experience to Dyne, most recently serving as vice president of rare genetic disease clinical development at Agios Pharmaceuticals, where he oversaw development across several hemolytic anemia indications. In his previous role as vice president of clinical development at Sarepta Therapeutics, he focused on advancing candidate therapies for rare neuromuscular disease. Dr. Mix received his B.A. in chemistry from Haverford College and his M.D. from the University of Massachusetts Medical School. He completed his residency in internal medicine at Tufts Medical Center, a fellowship in nephrology at the Beth Israel Deaconess Medical Center in Boston and an M.S. in clinical care research at the Tufts School of Biomedical Sciences.

Mr. Najim brings a wealth of CMC biopharmaceutical development and cGMP manufacturing experience across multiple biologic expression systems and small molecules. Mr. Najim previously held roles of increasing responsibility at Proteon Therapeutics, including most recently as vice president of manufacturing and process development, and also served as associate director of manufacturing at Dyax Corporation. He received his B.S. in biochemistry from Merrimack College and his MBA from Bentley University.

About Dyne TherapeuticsDyne Therapeutics is pioneering life-transforming therapies for patients with serious muscle diseases. The companys FORCE platform delivers oligonucleotides and other molecules to skeletal, cardiac and smooth muscle with unprecedented precision to restore muscle health. Dyne is advancing treatments for myotonic dystrophy type 1 (DM1), Duchenne muscular dystrophy (DMD) and facioscapulohumeral muscular dystrophy (FSHD). Dyne was founded by Atlas Venture and is headquartered in Waltham, Mass. For more information, please visit http://www.dyne-tx.com, and follow us on Twitter and LinkedIn.

Link:
Dyne Therapeutics Expands Leadership Team with Key Hires - Business Wire

54gene has announced the launch of the African Centre for Translational Genomics (ACTG), an initiative established to facilitate translational genomics research by African scientists.

This initiative is the coming together of leading scientists as a welcome development for leveraging talent from across Nigeria to promote genomics research scholarship.

The establishment will also re-invest in the health ecosystem by empowering the next generation of African genomic scientists through the provision and implementation of grants, fellowships, internships, and training for medical researchers, trainees, and students, the company said in a statement released on Tuesday, February 4th, 2020.

According to a 2018 National Center for Biotechnology Information (NCBI) report, Nigeria has few medical geneticists and genetic counselors in Nigeria with most genetic disorders patients seen by pediatricians.

With this first concerted effort from genetic scientists and researchers, the ACTG will be funding its first study under the Non-Communicable Diseases - Genetic Heritage Study (NCD-GHS) Consortium. The consortium will see over 100,000 Nigerians participate in the eponymous study which will seek to understand the genetic basis of the highly prevalent non-Communicable Diseases (NCDs) in Nigeria such as cancers, diabetes, Alzheimers, chronic kidney, sickle cell disease, among others.

ALSO READ: Business Insider chats with the CEO of 54gene, the company building the world's first pan-African biobank

The consortium will have a steering committee co-led by the Director-General of Nigeria Institute of Medical Research [NIMR], Prof. Babatunde Lawal Salako, the Director of National Biotechnology Development Agencys Centre for Genomics Research and Innovation [NABDA-CGRI], Prof Oyekanmi Nash, the CEO of 54gene, Dr. Abasi Ene-Obong, Dr. Segun Fatumo, Assistant Professor, London School of Hygiene and Tropical Medicine [LSHTM], and Dr. Omolola Salako, Consultant Oncologist, College of Medicine, University of Lagos [CMUL].

Speaking on the consortium launch, Dr. Abasi Ene-Obong, said, In continuation with our belief at 54gene that genetic research in Africa should be ethical and beneficial to the communities we serve, and that African scientists be at the forefront of new drug discoveries that benefit Africans and the world at large; we have set up the ACTG to harness translational genetic research across Africa. The NCD-GHS study is our pilot effort under the ACTG that has the potential to rewrite the playbook of genomics research, where African scientists will be placed at the forefront of new drug discoveries for conditions that affect the health of not only Nigerians but greater Africa and the world.

Our collaboration with scientists at NIMR and NABDA-CGRI, as a consortium, is a highly welcome initiative which we believe will be a rewarding and mutually beneficial experience for all parties. For 54gene specifically, the opportunity for us to contribute to a broader national agenda for genomics research is both inspiring and humbling, and we are committed to ensuring its success.

Joining Dr. Ene-Obong at the launch of the NCD-GHS Consortium included many of Nigerias most prominent geneticists and medical research professionals.

Professor. Babatunde Lawal Salako, Director General of the Nigeria Institute of Medical Research (NIMR), added that the consortium will engage senior scientists that have made their mark in the field of cardiometabolic research in teaching hospitals across the country to ensure representativeness and quality.

Read the original:
Nigerias most prominent geneticists and medical research professionals are coming together to promote genomics research and make new drug discoveries...

Austin was three years old and Max was a newborn when their mother, Jenn McNary, learned they had a rare genetic condition called Duchenne muscular dystrophy. The doctor painted a grim picture: Her boys would stop walking by age 12 or 13 and, shortly thereafter, they would require nighttime ventilation. They would each need a tracheotomy, a feeding tube, or both by their late teens. Death would come a few years later.

It hasn't worked out that way, thanks to two new drugs that became available after the boys' 2002 diagnosis. Exondys 51, a medicine that targets their genetic mutation, slows the disease's progression, and Emflaza, a corticosteroid, mitigates some of its symptoms. Thanks to these treatments, Austin now attends college and interns at a biotech company. Max attends his local high school in Newton, Massachusetts. Both are able to get around in wheelchairs, and neither needs ventilation. McNary just rented an apartment for her boys because they can function on their own with the help of an aide.

By all accounts, the drugs have been transformative, McNary said. But, she added, her boys "aren't going to be cured," and extending and improving their life for an unknown period of time comes at a high price. Emflaza came onto the market in 2017 at an annual cost of $65,000. Exondys 51 appeared in 2016 at $748,500. Neither of the drugs will help the young men walk again and, in the eyes of some U.S. health economists, the drugs are not worth the price.

That's why McNary hates the quality-adjusted life year (QALY, pronounced "qua-lee"), an economic calculation that attempts to quantify the value of a medical intervention, based in part on the quality of life it bestows on recipients.

First developed by U.S. economists in the late 1960s and early 1970s, variations of the QALY have been used for years by governments around the world to help determine what treatments citizens can obtain under public health care. In America's free-market health care system, however, QALY calculations have largely been avoided. As McNary and others like her are finding out, that's starting to change.

Advertisement:

As policymakers and insurance companies scramble to get a handle on skyrocketing health care costs, they are promoting the idea of paying for value. In this view, drugs designated as higher-value should be prioritized over lower-value treatments. But this raises a thorny question: Who gets to define "value"? Health economists and insurance companies who seek to use limited health care dollars judiciously? Or patients, parents, and doctors who want to receive the best health care for their situation?

Because the quality-adjusted life year threatens her sons' ability to get the medicine they need, McNary is clear about her answer. "To me, the QALY is a measurement that says that keeping my sons alive by providing incremental benefit but not totally curing them is never going to be valuable," McNary said. "Just mull that around in your head if you are less than perfect, you are worth less money."

* * *

In QALY math, a year of perfect health is equal to 1; death equates to 0. The value of other health states is derived from surveys of patients, caregivers, or the general public. Paralysis might be valued at .35, for example, and mild Alzheimer's disease at .52, depending on the survey. Those numbers can then be plugged into a formula that allows the relative cost-effectiveness of treatments to be compared to identify the best buys.

Economists developed the QALY concept more than 40 years ago to address a fundamental question: "Where should we spend whose money to undertake what programs to save which lives with what probability?' Richard J. Zeckhauser and Donald Shepard asked in a 1976 article describing the basic QALY formula. The next year, as U.S. health care spending topped $120 billion, Harvard health policy professor Milton C. Weinstein and his colleague, cardiologist William B. Stason, sounded an alarm bell. "It is now almost universally believed that the resources available to meet the demands for health care are limited," they wrote in the New England Journal of Medicine. "We, as a nation, will have to think very carefully about how to allocate the resources we are willing to make available for health care."

Their article cited by other authors more than a thousand times in the past four decades pointed out that resources were already being allocated by millions of individual decisions: hospitals rationing beds where they didn't have room for all patients, for example, and insurers agreeing to pay for some tests and treatments but not for others. Such decisions, they argued, were often inconsistent with the "societal objective of deriving the maximum health benefits from the dollars spent," an objective that could be achieved by putting the QALY to work.

In the intervening decades, some countries the United Kingdom, the Netherlands, and Sweden, for example have embraced QALY-based evaluations. In the U.K., cost-effectiveness studies are used, in part, to determine which therapies the National Health Service will provide for residents. The publicly-funded health system does not cover Orkambi, the first cystic fibrosis treatment that targets the cause of the disease, for example, because its cost-per-QALY far exceeds the U.K. cost-effectiveness threshold.

In the United States, however, QALY-based assessments have not gained traction until recently. "Perhaps the general reason is that we as patients and our providers don't want to be limited in the treatment options available," said Louis P. Garrison Jr., an economist in the Pharmaceutical Outcomes Research and Policy Program at the University of Washington.

In fact, QALY-based cost-effectiveness reviews are so controversial that the federal government has repeatedly quashed their use. In 1992, the Department of Health and Human Services rejected Oregon's attempt to use QALY-based cost-effectiveness assessments to determine what services its Medicaid program would cover. In 2010, as part of the Patient Protection and Affordable Care Act, Congress prohibited the use of QALYs by the Medicare program. It also banned the federal Patient-Centered Outcomes Research Institute from using QALY thresholds in its assessments of comparative treatments.

* * *

A QALY Primer

A QALY reflects quality of life and length of life. A year in "perfect health" is worth 1 QALY, death is worth 0 QALYs, and other health states fall between 0 and 1. The amount that a drug lengthens or improves the quality of life is calculated as "QALYs gained." The cost of getting a certain level of health improvement is the "cost per QALY gained," shown here for several interventions targeting asthma.

But more than half of U.S. residents are covered by private insurance companies, which are not prohibited from using QALY-based assessments to decide which medicines they will cover for their members. Traditionally, however, private insurers have generally not used QALYs explicitly in their decisions about what tests and treatments they will pay for, according to a recent report by the National Council on Disability. Instead, when major U.S. insurers decide to limit access to a given medication, they usually cite insufficient data to justify its use in a given situation.

Indeed, until recently, U.S. insurers did not have a source for QALY-based cost-effectiveness reports. That began to change in 2014, when the Institute for Clinical and Economic Review, a nonprofit research organization based in Boston, turned its attention to high-cost drugs. Founded in 2006 as a research project based at Harvard Medical School, ICER initially issued reports on broad topics such as obesity management and palliative care. But when Sovaldi, a drug for deadly hepatitis C, came on the market at the then-shocking price of $84,000 for a 12-week course of treatment, ICER kicked into action. Despite the high price, its assessment found that Sovaldi is cost-effective for some patients. Insurers took notice.

Since then, the organization has been churning out several drug-assessment reports each year. Each report includes its opinion of how much the drug is worth; drugs priced higher than that are deemed not cost-effective. ICER has no authority over anyone, but its reports have become popular reading for U.S. insurers. "If there is a drug of note being approved by the FDA, there's also likely going to be an ICER assessment of that drug that can factor into their decision-making," said David Whitrap, the research organization's vice president of communications and outreach.

* * *

U.S. health care spending has risen dramatically since Weinstein and Stason expressed concern in the mid-1970s. In 2016, the U.S. spent nearly 18 percent of its gross domestic product on health care, far outstripping the average of 11 percent for 10 other high-income nations. High prices for prescription drugs is one reason. "We're seeing price tags now of $1 million, $2 million," said Seema Verma, administrator for the federal Centers for Medicare and Medicaid Services, at a conference recently. "That's completely unsustainable for the system."

That's why Peter Neumann, director of the Center for the Evaluation of Value and Risk in Health at Tufts Medical Center, said cost-effectiveness analyses are needed more than ever. But there are many reasons for the resistance, Neumann and his co-authors wrote in the Journal of the American Medical Association, including "an inclination on the part of many individuals in the United States to minimize the underlying problem of resource scarcity and the consequent need to explicitly ration care."

Further, Ari Ne'eman, a disability rights activist and consultant to Partnership to Improve Patient Care, a coalition of advocacy groups, said the idea that two health conditions can be numerically compared to one another is simply wrong. "Proponents of the QALY will say it is this mathematically perfect measure that gives us a superpower ability to compare depression drugs to cystic fibrosis drugs to cancer drugs even though all of those drugs do different things because it lets you translate them back to this common measure," he said. "Our concern is that when you engage in that process of translation, you lose some significant nuance in terms of the amount of benefit that's being delivered."

The Partnership argues the QALY calculation is flawed because it assumes quality of life can be captured by a certain number, despite the fact that different surveys arrive at different numbers. For example, a 2006 quality-of-life survey in the U.S. assigns blindness/low vision as .69 on the 0-to-1 scale, while a 2011 survey in the U.K. gives blindness/low vision a score of .78.

Beyond the methodological issues, Ne'eman said, "there are all kinds of ethical problems with it." People with disabilities and chronic medical conditions may value a treatment that offers an incremental improvement in the quality or length of their lives, even though the "QALYs gained" are less than those for a treatment that prevents the loss of perfect health.

Former U.S. Representative Tony Coelho, a Democrat from California and a primary author of the Americans with Disabilities Act, is the Partnership's chairman. "I worry that more focus is being given to what is most cost-effective for the 'average patient' than creating a system that works for each individual patient," he wrote in 2018. "The medication I take for epilepsy isn't 'high value' for every patient. But it's the only one that works for me."

That's why, Ne'eman said, cost-effectiveness analyses must consider the fact that not all patients respond the same way to a drug. Some patients need drugs that aren't deemed cost-effective for the general population. It's important to account for that, he said. "Otherwise we're giving insurers a tool to deny care to people who need it."

When an insurer decides to cover a specific drug, that decision affects everybody who pays into the insurance pool. Michael Sherman, chief medical officer for the insurer Harvard Pilgrim Health Care, uses the example of a gene therapy that costs $1 million to treat a child who will die without it. Under the ACA, families will hit their out-of-pocket maximum at about $16,000, and many health plans have out-of-pocket maximums far below that. "The rest of that million dollars is going to be paid by everyone else that's the way it works in insurance," he said. When insurers see that kind of unanticipated budget impact, they raise premiums or out-of-pocket cost-sharing for everyone.

Like other proponents of the QALY, Neumann sees it as an imperfect but useful tool. "Any single number is never going to capture everything," he said.

"The problem is, if you're not going to use QALYs, what are you going to use?"

* * *

That's an urgent question, particularly now when there is a huge pipeline for rare-disease therapies, often called orphan drugs. By 2024, orphan drug sales are expected to reach $242 billion.

In the U.S., a rare disease is defined as one that affects fewer than 200,000 people. While these conditions are individually rare, in the aggregate, an estimated 25 to 30 million Americans that's about one in 10 live with a rare disease. Most rare diseases affect children, and many are fatal or disabling.

Historically, drugmakers spent little effort developing treatments for rare diseases, but that changed with the passage of the Orphan Drug Act of 1983, which provides tax credits and a seven-year marketing exclusivity to companies that develop rare-disease treatments. Hundreds of such treatments have won FDA approval in recent years, with more than 560 medicines in the works.

Those treatments are generally expensive. On average, the per-patient cost for orphan drugs in the U.S. is almost 4.5 times more than for non-orphan drugs.

In the two decades ending in 2017, the average annual cost for orphan drugs was $123,543, based on the price at the time the drug launched, compared to $4,961 for traditional drugs. For Duchenne alone, more than 30 orphan therapies are in development. None of them are going to cure patients, McNary said. But she hopes new treatments, generally used in combination, will help her sons live longer, healthier lives and completely change the disease trajectory for younger patients whose disease has not yet progressed as far.

The barrier she worries about is cost-effectiveness analysis. In August, the Institute for Clinical and Economic Review published its assessment of treatments for Duchenne, which affects about 400 to 600 boys born in the U.S. each year. Emflaza, the corticosteroid, appears to be as good as or better than prednisone, another corticosteroid approved to treat the disease, but it would need a price cut of at least 73 percent to be considered cost-effective.

Exondys 51 approved by the FDA for about 13 percent of the Duchenne population got a worse review. In the clinical trials used to seek FDA approval, no clinical benefit, including motor function improvement, was demonstrated. (The FDA approved the drug because some of the patients treated with Exondys 51 had a slight increase in dystrophin levels in skeletal muscle.) In light of that, Exondys 51 was not deemed cost-effective at any price.

But Jenn McNary said the drug works for her sons. Austin, who was not eligible for the Exondys 51 clinical trial, stopped walking at age 10. Max got in the trial and started taking the drug at age 9."They have the same mutation, they have been raised by the same mother, so one would expect they would progress similarly," she said. "But Max walked until he was 17."

Austin was already in a wheelchair when, at age 15, he started taking Exondys 51. He regained some upper-body strength that changed his life, according to his mother. "He's able to use a urinal on his own, which makes is possible for him to have a job and to go to college without an aide," she said.

The Medicaid program in Massachusetts, where the McNarys live, won't pay for Max's Duchenne therapies. For the time-being, the drugmakers are giving him the drugs free through a patient-assistance program. Austin, because he's enrolled in college, is eligible for student coverage through Blue Cross Blue Shield of Massachusetts. The insurer, by policy, does not cover Exondys 51 for patients who can no longer walk. His mother appeals the insurance denial. Every six months, she sends a video of Austin in action, along with a letter from his doctor and so far, his medicines have been covered.

The payers made their coverage policies before the quality-adjusted life year analysis was published. Now, insurers who have been covering the Duchenne treatments have an independent analysis with which to rethink that decision.

For now, there is one thing that QALY supporters and critics agree on. "Very promising drugs are coming, and they're going to be very expensive," said Neumann, the health economist at Tufts. Increasingly, the QALY appears poised to influence how American health care money is spent.

* * *

Lola Butcher is a health care business and policy writer based in Missouri.

This article was originally published on Undark. Read the original article.

Excerpt from:
Is the medication you're taking worth its price? - Salon

According to the American Academy of Dermatology, acne affects up to a staggering 50 million Americans annually.

To make matters worse, blackheads, whiteheads, pimples, cysts and other acne-related blemishes seem to occur at the most inconvenient times: before a date, a meeting, class photos, you name it. Although acne is not a serious health threat, severe acne can lead to disfiguring and permanent scarring.

Why do I have acne? Acne is most commonly linked to the changes in hormone levels during puberty, but can start at any age. Certain hormones cause the grease-producing glands next to hair follicles in the skin to produce larger amounts of oil, or abnormal sebum. This abnormal oil changes the activity of harmless skin bacterium called P. acnes, or propionibacterium acnes, which becomes more aggressive and causes inflammation and pus. Certain medications, stress and a poor diet can also contribute to acne. There is also evidence of a genetic component to acne as well.

Types of treatments: Because acne is caused by a myriad of factors, treating it with one product or medicine usually is not enough. You may need to attack it from many angles with different types of treatments that all work differently.

While a pimple will eventually go away, if you have numerous outbreaks, you could end up with scars. This is when it is time to visit a dermatologist, who may suggest a cream, lotion, gel or some that contains ingredients that can help. Many can be bought without a prescription:

Benzoyl peroxide kills bacteria and removes extra oil.

Salicylic acid keeps pores from getting clogged.

Sulfur removes dead skin cells.

Stronger treatments: If some of these over-the-counter remedies do not get your acne under control, your doctor may prescribe a retinoid to be used on the skin. This comes in a cream or gel and helps unplug oil ducts. Antibiotics in cream, lotion, solution or gel form may be used for inflammatory acne.

Isotretinoin is a medicine used to treat severe acne. It is usually used for cystic acne that does not improve after treatment with other medicines. Brand names include Accutane, Amnesteem, Sotret and Claravis. Isotretinoin is the most effective long-term medication for acne but is associated with some risks that dermatologists are familiar with. Spironolactone blocks excess hormones.

When to seek medical help: Even mild cases of acne can cause distress and, in some cases, depression. If your acne is making you feel unhappy or you are having a hard time controlling your blemishes with over-the-counter medication, see your doctor. Try to resist the temptation to pick or squeeze the spots, because this can lead to scarring.

Treatments can take a few months to work, so do not expect immediate results. Once they do start to work, the results are usually good.

Dr. Daniel Shurman of Pennsylvania Dermatology Partners in Amity Township completed his dermatology training at Thomas Jefferson University. He is fellowship-trained in both Mohs micrographic surgery and procedural dermatology, and his research interests include medical genetics, antibiotics in dermatologic surgery and wound healing.

The rest is here:
Here are some tips, treatment options for acne - The Reporter

As the 2019 novel coronavirus outbreak continues to spreadin China, researchers have found that people carrying the virus but not showingsymptoms may be able to infect others.

If infected people can spread 2019-nCoV while asymptomatic,it could be harder to trace contacts and contain the epidemic, which is alreadya globalhealth emergency (SN: 1/30/20).

An unnamed Shanghai woman passed the virus to businesscolleagues in Germanybefore she showed signs of the illness, doctors report January 30 in the New England Journal of Medicine. Thewoman had attended a business meeting at the headquarters of the auto supplierWebasto in Stockdorf on January 20 and flew back to China on January 22. Shebecame ill with mild symptoms on the flight back to China and tested positivefor the virus.

Meanwhile, one of her German colleagues fell ill on January24 with a fever, sore throat, chills and muscle aches. His illness was brief,and he returned to work on January 27, the same day that the woman informed thecompany she carried the virus. Nasal swabs and sputum, or phlegm, samples fromthe man contained high levels of the novel coronavirus even though his symptomshad passed.

Headlines and summaries of the latest Science News articles, delivered to your inbox

Three other employees of the company also tested positivefor the virus. Tracing their contacts, doctors conclude that the first man andanother person caught the virus from their Chinese colleague.

Whats also concerning is that the first man apparently passedthe virus to the other two coworkers, who both had contact with him before hedeveloped symptoms. All cases of the illness have been mild.

These cases suggest that people shed the virus before theyshow symptoms and after recovery from the illness, say Camilla Rothe, atropical medicine and infectious disease specialist at the University Hospital ofLudwig-Maximilians-Universitt in Munich, and her colleagues.

Asymptomatic spread, though common for influenza viruses forexample, would be a new trick for coronaviruses. The coronaviruses that causesevere acute respiratory syndrome, or SARS, and Middle East respiratorysyndrome, or MERS, are notcontagious before people show symptoms (SN:1/28/20).

Another coworker of the firm was confirmed to have the viruson January 30, and a child of one of the infected workers has also contractedthe virus, bringing the case count to six, health officials in the German stateof Bavaria said January 31. The company has closed its headquarters near Munichuntil February 2 and began testing contacts of the ill employees on January 29.

Visit link:
The first case of coronavirus being spread by a person with no symptoms has been found - Science News

Before a packed room at the Health Sciences Learning Center on the University of WisconsinMadison campus on Jan. 29, Associate Dean for Public Health and Community Engagement Jonathan Temte asked for a moment of silence for those affected by an outbreak of a virus that in a matter of weeks has sickened nearly 10,000 people around the world and killed more than 200 people in China as of Jan. 31.

The virus, a previously unknown member of a class of coronaviruses, was first described in late December 2019 after several cases of illness appeared in people in Wuhan, a city in Hubei province, China. Its name, for now, is 2019-nCoV.

As details of the virus and its effects continue to emerge, UWMadison gathered a panel of experts, including physicians, epidemiologists, public health officials, scientists and communication experts, to address questions and concerns from the public.

Watch a video of the livestreamed event.

The event came together on short notice after the director of the Centers for Disease Control and Prevention, Robert R. Redfield, had to cancel his previously scheduled talk in Madison in order to help manage the outbreak.

Here are some takeaways:

Coronaviruses are relatively common. What makes this coronavirus unique is that it has never been implicated in human disease before. There are several human coronaviruses that cause mild disease and we have known about them for decades now, said Kristen Bernard, a professor in the UW School of Veterinary Medicine. They are the cause for about 30 percent of common colds. They are also the viruses behind the 2003 SARS and 2012 MERS outbreaks, which both killed large numbers of people.

The original source of the virus is probably bats, which serve as a reservoir for large numbers of zoonotic diseases, or those that pass between animals and people. Most of these viruses rely on an intermediary species to render it infectious in people. With SARS, experts believe that species was civet cats, and with MERS, it was dromedary camels. Some early reports blamed snakes for the 2019-nCoV outbreak, but, said Chris Olsen, emeritus professor in the School of Veterinary Medicine: I think we need to take that with a very large grain of salt.

In people, 2019-nCoV is transmitted through coughing and contact with saliva, mucus or the tears of people sick with the virus. Symptoms of illness include cough, fever and shortness of breath. Public health officials are still working to determine whether infected people can transmit the virus to others if they are not symptomatic.

There have been six confirmed cases of 2019-nCoV in the United States since mid-January, and as of Jan. 30, officials in the U.S. reported the first case of person-to-person transmission. There have been no confirmed cases in Wisconsin, though experts continue to monitor patients for symptoms and have sent six potential cases to the CDC for testing. One came back negative for the virus and results are still pending on the remaining samples. Allen Bateman, assistant director in the communicable disease division of the Wisconsin State Lab of Hygiene, said the laboratory is working with local health departments and clinical labs across the state to help with testing and response.

There are no specific cures or treatments for people with 2019-nCoV, but as is the case with many viruses, said Medical Director of Infection Control at UW Hospital and Clinics Nasia Safdar, those who are sick are offered supportive care to relieve symptoms and mitigate complications. And because the symptoms of the novel coronavirus are similar to other kinds of viruses, she and colleagues are working with health care providers to train them on containment and help keep them safe.

There are no cases of 2019-nCoV in Wisconsin at this time, but we are prepared to react if things are changing, said Patrick Kelly, interim director of medical services at University Health Services. On campus, that has meant taking steps to keep more than 40,000 students safe and provide physical and mental health care as needed. It has also meant communicating often with students and their families. An all-campus message sent Jan. 24 shared information about the novel virus and was translated on short notice in five languages.

The state has also been working on the logistics of monitoring and preparing for the virus, said School of Medicine and Public Health (SMPH) Professor of Medicine Ryan Westergaard, also chief medical officer and state epidemiologist at the Wisconsin Department of Health Services. While some areas have couriers to transport samples from the clinic to the state lab for testing, police are serving that role in others. Its been a good learning experience, he said, with people from legislative offices and the governors office at the table to make sure we are coordinating well.

Its important to be prepared for a possible outbreak of coronavirus, but public health officials still remain more concerned about seasonal influenza. That virus has had a greater impact in Wisconsin, and in the U.S., so far this year. Right now, in Dane County and southern Wisconsin, were in the midst of a huge influenza outbreak, said Temte, also a family medicine physician. As of Friday (Jan. 24), 54 children across the country had died of influenza and influenza is one of these diseases for which we have effective vaccines and effective antivirals.

Scientists at UWMadison are monitoring research developments globally. Chinese scientists worked swiftly in the aftermath of the outbreak to decode the genetic sequence of 2019-nCoV and share it with other researchers worldwide. Thomas Friedrich, a professor in the School of Veterinary Medicine, said some researchers are working with that sequence to develop vaccines against the new coronavirus. Some journals where scientists publish, including the New England Journal of Medicine, require researchers to share their raw data for others to use, and many researchers are making data instantly available on widely-used pre-print servers. I think its very important for us to make our information available to the public as much as possible, he said.

Misinformation is easy to spread, so sticking with facts when discussing 2019-nCoV is imperative, said Emily Kumlien, media strategist at UW Health. We work with the experts to get the right information to share with the community at the right time. That includes using social media and other platforms to reach people in the places where they get their news, and where misinformation is most likely to live. I think its everybodys responsibility, said Ajay Sethi, SMPH professor of population health, to serve as educated, informed opinion leaders; to identify misinformation; and to find creative and strategic ways to dispel that.

Officials believe the novel coronavirus originated in a seafood and live animal market in Wuhan. But shutting down these kinds of markets broadly would be akin to telling Wisconsinites not to hunt deer, said Bernard. Thats part of their culture and we have to be sensitive to that. However, she added: There are things we can do and thats why basic research is so, so important.

Excerpt from:
Here is what you need to know about novel... - ScienceBlog.com

It involves milking snake venom by hand and injecting it into horses or other animals in small doses to evoke an immune response. The animal's blood is drawn and purified to obtain antibodies that act against the venom.

Producing antivenom in this way can get messy, not to mention dangerous. The process is error prone, laborious and the finished serum can result in serious side effects.

Experts have long called for better ways to treat snake bites, which kill some 200 people a day.

Now -- finally -- scientists are applying stem cell research and genome mapping to this long-ignored field of research. They hope it will bring antivenom production into the 21st Century and ultimately save thousands, if not hundreds of thousands, of lives each year.

Researchers in the Netherlands have created venom-producing glands from the Cape Coral Snake and eight other snake species in the lab, using stem cells. The toxins produced by the miniature 3-D replicas of snake glands are all but identical to the snake's venom, the team announced Thursday.

"They've really moved the game on," said Nick Cammack, head of the snakebite team at UK medical research charity Wellcome. "These are massive developments because it's bringing 2020 science into a field that's been neglected."

Hans Clevers, the principal investigator at the Hubrecht Institute for Developmental Biology and Stem Cell Research in Utrecht, never expected to be using his lab to make snake venom.

So why did he decide to culture a snake venom gland?

Clevers said it was essentially a whim of three PhD students working in his lab who'd grown bored of reproducing mouse and human kidneys, livers and guts. "I think they sat down and asked themselves what is the most iconic animal we can culture? Not human or mouse. They said it's got to be the snake. The snake venom gland."

"They assumed that snakes would have stem cells the same way mice and humans have stems cells but nobody had ever investigated this," said Clevers.

After sourcing some fertilized snake eggs from a dealer, the researchers found they were able to take a tiny chunk of snake tissue, containing stem cells, and nurture it in a dish with the same growth factor they used for human organoids -- albeit at a lower temperature -- to create the venom glands. And they found that these snake organoids -- tiny balls just one millimeter wide -- produced the same toxins as the snake venom.

The team compared their lab-made venom with the real thing at the genetic level and in terms of function, finding that muscle cells stopped firing when exposed to their synthetic venom.

The current antivenoms available to us, produced in horses not humans, trigger relatively high rates of adverse reactions, which can be mild, like rash and itch, or more serious, like anaphylaxis. It's also expensive stuff. Wellcome estimate that one vial of antivenom costs $160, and a full course usually requires multiple vials.

Even if the people who need it can afford it -- most snakebite victims live in rural Asia and Africa -- the world has less than half of the antivenom stock it needs, according to Wellcome. Plus antivenoms have been developed for only around 60% of the world's venomous snakes.

In this context, the new research could have far-reaching consequences, allowing scientists to create a biobank of snake gland organoids from the 600 or so venomous snake species that could be used to produce limitless amounts of snake venom in a lab, said Clevers.

"The next step is to take all that knowledge and start investigating new antivenoms that take a more molecular approach," said Clevers.

To create an antivenom, genetic information and organoid technology could be used to make the specific venom components that cause the most harm -- and from them produce monoclonal antibodies, which mimic the body's immune system, to fight the venom, a method already used in immunotherapy treatments for cancer and other diseases.

"It's a great new way to work with venom in terms of developing new treatments and developing antivenom. Snakes are very difficult to look after," Cammack said, who was not involved with the research.

Clevers said his lab now plans to make venom gland organoids from the world's 50 most venomous animals and they will share this biobank with researchers worldwide. At the moment, Clevers said they are able to produce the organoids at a rate of one a week.

But producing antivenom is not an area that pharmaceutical companies have traditionally been keen to invest in, Clevers said

Campaigners often describe snakebites as a hidden health crisis, with snakebites killing more people than prostrate cancer and cholera worldwide, Cammack said.

"There's no money in the countries that suffer. Don't underestimate how many people die. Sharks kill about 20 per year. Snakes kill 100,000 or 150,000," said Clevers.

"I'm a cancer researcher essentially and I am appalled by the difference in investment in cancer research and this research."

One challenge to making synthetic antivenom is the sheer complexity of how a snake disables its prey. Its venom contains several different components that have different effects.

Researchers in India have sequenced the genome of the Indian Cobra, in an attempt to decode the venom.

"It's the first time a very medically important snake has been mapped in such detail," said Somasekar Seshagiri, president of SciGenom Research Foundation, a nonprofit research center in India.

"It creates the blueprint of the snake and helps us get the information from the venom glands." Next, his team will map the genomes of the saw-scaled viper, the common krait and the Russell's viper -- the rest of India's "big four." This could help make antivenom from the glands as it will be easier to identify the right proteins.

In tandem, both breakthroughs will also make it easier to discover whether some of the potent molecules contained in snake venom are themselves worth prospecting as drugs -- allowing snakes to make their mark on human health in a different way to how nature intended -- by saving lives.

"As well as being scary, venom is amazingly useful," Seshagari said.

The rest is here:
Snake venom can now be made in a lab and that could save many lives - CNN

Ethnic and racial minority populations in the U.S. have a long history of being mistreated by the health care system, researchers and the government. The resulting mistrust can pose a challenge for researchers seeking to understand the biology of complex traits, as well as for physicians interested in delivering personalized care to diverse patients. Diversity in precision medicine research is crucial for understanding genetic differences that shape so many health outcomes and potential treatments.

Learn what physicians and health systems can do to advance precision medicine research and build rapport and trust to increase minority participation in critical research.

Genetics and precision medicine have become increasingly important in effective patient care. Through its partnerships and research, the AMA is advancing the ethical implementation of precision medicine.

About 10% of the worlds population is of European ancestry. However, this population accounts for 78% of genetic study participants. The National Institutes of Healths All of Us Research Program aims to address this disparity in medical research by enrolling 1 million or more participants to gather data on a wide variety of health conditions.

The AMA has partnered with the All of Us program, which aims to enable a new era of medicine through research, technology, and policies that empower patients, researchers and providers to work together to develop individualized care. This program is intended to gain better insights into the biological, environmental and behavioral influences on disease to enhance prevention and treatment.

The AMA Ed Hub module, All of Us Research Program: Informing the Future of Health Care, is enduring material and designated by the AMA for a maximum of 0.75 AMA PRA Category 1 Credit.

Learn more about AMA CME accreditation.

There are currently more than 320,000 All of Us participants, with about 250,000 having completed the initial steps of the program. Nationwide, more than 50% of All of Us participants are members of racial or ethnic minority groups. And in Illinois, more than 80% are from groups that have traditionally been underrepresented in biomedical research.

Joyce Ho, PhD, is a research assistant professor and lead investigator for the All of Us Research Program at Northwestern University Feinberg School of Medicine in Chicago. Ho shared how she and her colleagues in Illinois are engaging a diverse pool of participants, and offered advice for how physicians can help.

Were on track to build a sample of 1 million or more participants in the next five years or so, said Ho, adding that Illinois has more than 26,000 participants in the All of Us program to date. The Illinois Precision Medicine Consortium, which includes the University of Illinois, University of Chicago, Rush University Medical Center, NorthShore University Health System, and Cook County Health, is also in the lead nationally for how diverse their participant pool is.

The effort thats needed to reach diverse populations is something that we were prepared to put in, she said. We understood just from the history of research in this countryespecially with underrepresented populationsthat its not just, Hey, heres a consent form, please read it and we know you will participate.

Instead, trust must be built through providing honest and accurate answers to patients questions about precision medicine, the privacy and security of patients data, and more.

Those are all concepts that, regardless of how much you know about biomedical research, or whether you have participated in studies, you deserve a thorough explanation, said Ho.

Learn how to answer patients top five questions about the All of Us Research Program.

The actions of past medical researchers have earned much distrust in minority communities, making it crucial to treat these diverse populations as partners.

Nationally, even at the beginning of designing the All of Us Research Programbecause we know that we have this goal of building a diverse research databasewe made sure that participants are our partners, said Ho.

Participants from all walks of life should be included and valued in the design of the program. Everyone plays a major role.

The National Institutes of Health and its All of Us Research Program partners conducted focus groups to look at everything from participating in research to concepts about precision medicine and sharing data, said Ho. Theres a lot of work ... that we put in to understand how we can really build this resource in a way that includes what different communities want so that we really can benefit the health of people who are living in this country.

One of the most important ways that All of Us Research Program researchers in Illinois have approached this program is in the collaboration of community organizations, health systems and participants. All of Us Research Program investigators in Illinois have decades of experience working with diverse communities in biomedical research.

Transportation is often a barrier to working with underrepresented communities. It can prevent patients from receiving the health care they need. In Illinois, though, mobile clinical research units have allowed researchers to better reach these communities.

Researchers drive these research vehicles containing exam rooms to different communities to engage people about the program. They also leverage long-standing relationships with area churches, community organizations and clinics to engage community members.

That breaks down a lot of the barriers with transportation that happens in many of the communities here in Chicago, said Ho. It really makes a big difference in terms of being able to reach this community.

Engagement is keyin creating a diverse community of participants for precision medicine and biomedical research.

When we go out to talk to folks, we dont immediately ask people to participate. A lot of times, we just have great conversations with people about biomedical research, said Ho. A lot of times we are addressing a potential mistrust that has very reasonably existed in different communities.

For example, the University of Chicago has developed curriculum aimed at addressing mistrust, biomedical research and importance of research inclusion, especially among the African American community.

Our teams develop different engagement tools and strategies to reach communities that have been underrepresented in research, she said, adding that it goes beyond talking to someone for five or 10 minutes before they participate.

Instead, it is multiple conversations over time, and letting participants know that we aim to return health information back to them and perhaps in the future, they might decide to participate, said Ho.

And once participants have shared their information, it is important to reiterate that there will be a waiting period.

One of the challenges is to really explain to participants this is a long-term program and it really takes a lot of time and patience for us to be able to return the value back to you that you deserve, she said.

One of the missions of the program is not just building 1 million people and collecting all this data. Its just to have substantive conversations with people about the importance of inclusion in biomedical research to build awareness, she said.

By creating awareness around precision medicine and building trust within these communities, it is paving the way for future conversations.

Even if theyre being approached by another research group, theyll have a little more trust and understanding about why participation and representation is so important, said Ho.

Illinois All of Us researchers also have a community participant advisory board that provides feedback on the program. Together they discuss additional ways to engage Illinois communities.

These meetings cover items such as how to provide clinically relevant information to participants, which is one of the hallmarks of the program, Ho said. Were not just grabbing the data. Were also planning to return information back to participants.

Not only does the program have a 1-million-person database to build, but they need to have an infrastructure that is ready to process the volume of data and biosamples, while also prioritizing data security and privacy.

Our program spends a lot of resources building as secure of a data system as possible, said Ho, adding that there is also a whole pipeline of generating genomic data and clinically relevant data to return to participants.

Many people are wondering about the security and privacy of the data, so we need to not just build a very secure system, but be able to explain to people what the risks might be so that people can make an informed decision, she said.

One way that the All of Us program is building a robust research resource, is to include EHR data from participants. However, it is important for participants and physicians to know that the data is securely sharedall personal identifiable information is removed.

Data collected will be connected to other data types such as self-reported information, which includes health background and behaviors, as well as medical history, physical measurements and data gleaned from biosamples.

Theres a wide variety of longitudinal data were collecting from participants. Through a research data portal that the program is building, researchers will eventually be able to access data and samples to accelerate medical discoveries for diverse populations. Thats powerful, said Ho.

View post:
7 ways to expand diversity in precision medicine research - American Medical Association

It is important to note that a pill to cure HIV is not simply around the corner, Dr. David Margolis, director of the UNC HIV Cure Center, said.

Some of the challenges of the virus include how it integrates itself into the genetic material of human cells, Chahroudi said.

"In a way, it becomes a foreign gene that is living in the human cell," Margolis said. "That cell looks like any other cell in the body, so there is no drug or immune response that can see it. Once the sleeping virus is re-awoken, it spreads."

The long-lived persistence of the HIV virus in the body makes it difficult to eradicate, due to latently infected cells that escape the bodys immune system, according to UNC's HIV Cure Center.

When it is silent and integrated into the host cell genome, it is not visible to the immune system, and so the immune system basically doesnt have a way to attack it when its in this latent form, Chahroudi said.

People who are infected with HIV and treated with standard antiviral treatment which is effective at suppressing virus replication are still at risk by HIVs nature, Chahroudi said.

In order to try to enable the immune system to now be able to see the virus in patients or monkeys or mice who are treated with AVT you need to test different approaches to try to reverse that latency, Chahroudi said. That basically means reawakening the virus, or activating the virus, in order to now express viral antigens that can be seen and targeting by the immune system.

The work on this project began in conjunction with the beginning of the UNC and ViiV Healthcare Limited partnership, said Richard Dunham, adjunct assistant professor in the UNC HIV Cure Center and director at ViiV Healthcare.

Its really born at the interface of industry, academia, here at Qura," Dunham said. "We started on this work back in 2016/2017 and then worked our way from the lab to the mouse to the monkey over the last several years.

Chahroudi said that despite the new research discoveries, no cure has been discovered.

Neither of them was able to reduce the level of what we call reservoirs, which is basically a persistent virus that's in cells, Chahroudi said.

Dunham said that about five years ago, UNC and ViiV Healthcare came to the realization that they could make more substantial progress toward curing HIV by working together. In the years that followed, the institutions created Qura Therapeutics and the UNC HIV Cure Center to conduct research.

Emory University's HIV research team was added to further the partnership.

The overall principle here is that no one entity is really going to make that progress against HIV," Dunham said. "We feel like this partnership between industry and academia might help us to take these different and diverse approaches between the two types of organizations to work together to find an HIV cure."

Chahroudi said the next steps for the research include combining both of the latency-reversing strategies discovered at UNC and Emory to boost the immune response against the affected cells.

If were able to reawaken or reactive the virus and then treat the animals with different immune-boosting or aiding strategies, we hope that combination may have an impact on the level of virus reservoirs, Chahroudi said.

The goal for researchers at UNC is to make the chemical that treats latent cells into a drug that can be used in people, Margolis said.

university@dailytarheel.com

Read more:
UNC researchers contribute to breakthrough in HIV cure research - The Daily Tar Heel

Researchers at Harvard Medical School and Boston Children's Hospital have found a potential treatment for hereditary deafness, the same condition thought to have caused Ludwig van Beethoven to lose his hearing.

The scientists are using a new gene-editing approach that they say could someday prevent profound hearing loss.

Beethoven's Symphony No. 5 is a cornerstone of classical music. It is hard to believe the composer was almost completely deaf from a genetic condition when he finished it.

"These children are born fairly normal, but then over 10 or 20 years, they lose their hearing," Harvard neurobiology professor Dr. David Corey.

Aptly named "Beethoven mice" might hold the key to a potential cure. Scientists believe the animals have a defect in the same gene that may have caused Beethoven's deafness.

"Our genome is composed of about 3 billion letters of DNA that together make up 20,000 genes," Corey explained. "For the disease we're studying, one mistake in the DNA in one of the genes causes deafness."

Researchers identified that hearing gene called TMC1. It's a gene that comes in pairs.

Using a newly refined gene-editing system, they disabled the defective copy of the TMC1 gene, leaving the good gene in place.

"By eliminating just the bad copy, that would be sufficient to preserve hearing," Corey said.

The scientists then delivered the edited DNA back into the cells of the mice and tested their hearing.

"We put little scalp electrodes on the back of the head, play sounds into the ear and can measure the brain activity in response," Boston Children's Hospital professor of otolaryngology Dr. Jeffrey Holt said.

Researchers say the mice were able to hear sounds as low as 45 decibels, the level of a quiet conversation.

"This could be life-changing," Holt said.

A famed composer, his namesake mice and a team of scientists are using cutting-edge medicine to help people who would otherwise go deaf.

The scientists say this research paves the way for using the new editing system to treat as many as 3,500 other genetic diseases that are caused by one defective copy of a gene.

It's important to note that Holt holds patents on TMC1 gene therapy.

MEDICAL BREAKTHROUGHSRESEARCH SUMMARYTOPIC: BEETHOVEN MICE PREVENT DEAFNESS: MEDICINE'S NEXT BIG THING?REPORT: MB #4689

BACKGROUND: In the United States, hearing loss affects 48 million people and can occur at birth or develop at any age. One out of three people over the age 65 have some degree of hearing loss, and two out of three people over the age 75 have a hearing loss. Children in the United States are estimated at 3 million in having a hearing loss, and of those, 1.3 million are under the age of three. One of the leading causes of hearing loss is noise, and while preventable, can be permanent. Listening to a noisy subway for just 15 minutes a day over time can cause permanent damage to one's hearing. Listening to music on a smartphone at high volumes over time can cause permanent damage to one's hearing as well. The number of people with hearing loss is more than those living with Parkinson's, epilepsy, Alzheimer's, and diabetes combined. (Source: https://chchearing.org/facts-about-hearing-loss/ and https://hearinghealthfoundation.org/hearing-loss-tinnitus-statistics/)

TREATMENTS: The treatment you receive will depend on the cause and severity of the hearing loss. A reversible cause of hearing loss is earwax blockage where your doctor may remove earwax using suction or a small tool with a loop on the end. Some types of hearing loss can be treated with surgery, including abnormalities of the ear drum or bones of hearing (ossicles). Repeated infections with persistent fluid may result in your doctor inserting small tubes to help your ears drain. If your hearing loss is due to damage to your inner ear, a hearing aid can be helpful. With more severe hearing loss and limited benefit from conventional hearing aids, a cochlear implant may be an option. Unlike a hearing aid that amplifies sound and directs it into your ear canal, a cochlear implant bypasses damaged or nonworking parts of your inner ear and directly stimulates the hearing nerve. (Source: https://www.mayoclinic.org/diseases-conditions/hearing-loss/diagnosis-treatment/drc-20373077)

GENE EDITING WITH CRISPR: Scientists at Harvard Medical School and Boston Children's Hospital have used a newly tailored gene-editing approach in mice thought to have the same genetic defect that caused famed composer Beethoven to go deaf in adulthood. CRISPR-Cas9 gene editing works by using a molecule to identify the mutant DNA sequence. Once the system pinpoints the mutated DNA, the cutting enzyme, or Cas9, "snips" it; however, the gene editors are not always accurate. Sometimes, the guide RNA that leads the enzyme to the target site and the Cas9 enzyme are not precise and could cut the wrong DNA. The Harvard and Boston Children's scientists are using a modified Cas9 enzyme derived from Staphylococcus aureus bacteria that they are finding is significantly more accurate. (Source: https://hms.harvard.edu/news/saving-beethoven)

See the original post:
'Beethoven mice' prevent deafness: Medicine's next big thing? - WNDU-TV

SAN DIEGO, January 31, 2020Human Longevity, Inc.(HLI),an innovator in providing data-driven health intelligence and precision health to physicians and patients, announced the publication of a ground-breaking study in the journalProceedings of the National Academy of Sciences(PNAS). The study titled, Precision medicine integrating whole-genome sequencing, comprehensive metabolomics, and advanced imaging, showed thatby integrating whole-genome sequencing with advanced imaging and blood metabolites, clinicians identified adults at risk for key health conditions.Data from 1190 self-referred individuals evaluated with HLIs multi-modal precision health platform, Health Nucleus, show clinically significant findings associated with age-related chronic conditions including cancer, heart disease, diabetes, chronic liver disease, and neurological disorders leading causes of pre-mature mortality in adults.

The goal of precision medicine is to provide a path to assist physicians in achieving disease prevention and implementing accurate treatment strategies, said C. Thomas Caskey, MD, FACP, FACMG, FRSC, chief medical officer for Human Longevity, Inc., lead author of the study, and a member of the National Academy of Sciences. Our study showed that by employing a holistic and data-driven health assessment for each individual, we are able to achieve early disease detection in adults.

Study highlights include:

This study shows that the definition of healthy may not be what we think it is and depends upon a comprehensive health evaluation, said J. Craig Venter, PhD, founder, Human Longevity, Inc. and a member of the National Academy of Sciences. The data underscore Human Longevitys innovative approach to helping clinicians with early detection and personalized treatments, potentially achieving better health outcomes for patients.

Our traditional approach to the annual health assessment has been very superficial and will need to be replaced by data-driven measures that will be made possible as costs continue to decline for whole- genome sequencing, advanced imaging, especially MRI, and specialized blood analytics, said David Karow, MD, PhD, president and chief innovation officer, Human Longevity, Inc.

ABOUT THE STUDY

The study cohort was composed of 1190 self-referred participants who enrolled at Health Nucleuswith a median age of 54 y (range 20 to 89+ y, 33.8% female, 70.6% European). A multidisciplinary team, including cardiologists, radiologists, primary care physicians, clinical geneticists, genetic counselors, and research scientists, integrated deep phenotype data with genome data for each study participant.Participants were enrolled in the study between September 2015 and March 2018.

ABOUT THE HEALTH NUCLEUS

Health Nucleus is Human Longevitys premier health intelligence platform utilizing state-of-the-art technology to provide an assessment of current and future risk for cardiac, oncologic, metabolic, and cognitive diseases and conditions. This is provided through a proprietary, multi-modal approach, integrating data from an individuals whole-genome sequencing, brain and body MRI imaging, cardiac CT calcium scan, metabolomics, advanced blood test, and more. The health assessment is conducted at Human Longevitys Health Nucleus precision medicine center in La Jolla, California.For more information, visitwww.healthnucleus.com.

ABOUT HUMAN LONGEVITY

Human Longevity, Inc. (HLI)is a genomics-based,health intelligence companyempowering proactive healthcare and enabling a life better lived. HLIs business focus includes the Health Nucleus, a genomic-powered, precision medicine center which uses whole-genome sequencing analysis, advanced imaging, and blood analytics, to deliver the most complete picture of individual health. For more information, visitwww.humanlongevity.com.

# # #

For more information, contact: Debbie Feinberg, VP of Marketing, Human Longevity, Inc., 858-864-1058,dfeinberg@humanlongevity.com

See the original post:
Human Longevity's Largest Study of its Kind Shows Early Detection of Disease and Disease Risks in Adults - Cath Lab Digest

Photo Submitted

Dr. Mahendran Mahadevan, a professor in the Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences, willspeakfrom 3-4 p.m. Monday, Feb.3, in Room D2 of the Food Science Building, 2650 N. Young Ave. His presentation, "Food, Health, and Disease,"is open to everyone.

Mahadevan's presentation will focus on how different types of food and beverages plays a role in human body's health defense systems (Angiogenesis, stem cells/regeneration, microbiome, DNA protection, and immunity). This basic biological knowledge related to foods will be useful for better understanding about the effects of foods on the prevention and management of human diseases.

Mahadevan's research interests include: 1) roles of genetics, obesity, nutrition, food supplements, nutraceuticals, physical activity and other environmental/life style factors on prevention/public health and maternal, fetal, and child health; 2) tissue banking; 3) embryo and stem cell culture/expansion (particularly culture medium/conditions); and 4) gene therapy and stem cell gene therapy particularly in cancer and genetic diseases.

Mahadevan received his Veterinary medicine degree in 1975 from University of Ceylon Peradeniya, Sri Lanka and his doctoral degree in Reproductive biology from Monash University, Australia in 1982. His academic experience includes faculty positions in the Department of Physiology, School of medicine at the University of Ceylon and in the Department of Obstetrics and Gynecology at the University of Arkansas for Medical Sciences.

View original post here:
UAMS Professor to Present Relationships Among Food, Health, and Disease in Food Science Seminar - University of Arkansas Newswire

With the NFL Championship game this Sunday, all eyes turn to Whitehouse native and Kansas City Chiefs quarterback Patrick Mahomes.

Over the course of the last couple weeks, CBS19 has spoken to everyone from Mahomes father, Pat Mahomes Senior, his trainer at APEC, Bobby Stroupe, and fans across the region. Mahomes environment clearly helped forge him into a future NFL MVP.

Dr. Ushimbra Buford, a psychiatrist at UT Health Science Center at Tyler says there are crucial mental aspects of becoming an elite athlete.

Buford says the phrase nature vs nurture which references conflicting theories on whether the natural instincts with which people are born or the environment in which they are brought up has more of an impact on their development, is now somewhat outdated.

When I first started in medicine, we used to say things like nature and nurture and saw them as two different things. In the past several years with the advent and understanding of epigenetics, we understand now that the nurture aspect influences the nature, the environment influences your genetics, Buford said.

Buford says a persons development in all aspects, including athleticism, is heavily influenced by their environment, down to changes their body makes at a biological level.

From a genetic standpoint, that person may have a certain kind of capacity for the muscle fibers that they will produce that they were born with. But then they get into an environment where the expectation and the understanding and like the daily living is different from what their body is genetically set. Over time, their composition would change to reflect the activities they were involved in, and the potential reality exists that over time their genetics would change to reflect the new physical reality, Buford said.

This means growing up in an environment, such as in Mahomes case, where his father is a professional baseball player and he was immediately around athletics, can be incredibly beneficial. However, Buford says in athletics and in life, it always comes down to a choice to strive for greatness.

Every quarterback is saying we're going to the Super Bowl this year, but how many of them believe that?" Buford said. "How many of them really, truly feel that this is my going to be my reality? You almost have to be delusional like that to achieve greatness in a sense. You have to see and believe something before other people can or will."

This mentality is something everyone can implement in their daily lives. Buford says the sky is the limit when a persons head is in the right place.

We all have the ability to be incredible," Buford said. "You know, we really limit ourselves and I don't know if this is a societal thing, or it's just not receiving the right messages early enough in life. But don't ever think for a minute that anyone cannot become what they want to be. Only person stopping you is you.

RELATED: CHIEFS DAY: Whitehouse ISD wears red, gold in support of Patrick Mahomes' first Super Bowl

RELATED: Patrick Mahomes' foundation '15 and the Mahomies' helping kids achieve their dreams

RELATED: Patrick Mahomes' high school baseball coach: He is 'just an unbelievable athlete'

RELATED: Mahomes & Friends: KC Chiefs QB close with his hometown buddies

RELATED: Whitehouse alum designs Patrick Mahomes inspired ties

Original post:
The mental game: Inside the mind of an elite athlete - CBS19.tv KYTX

Investment Thesis

Objective: Wealth-building of an always fully-invested portfolio via repeated near-term (weeks or months) capital gains from careful, diversified, odds-on issue selection and timely price opportunity capture.

The stocks compared here are Sarepta Therapeutics, Inc. (NASDAQ:SRPT) and Arrowhead Pharmaceuticals Inc. (NASDAQ:ARWR). SRPT was inadvertently omitted from the Biotech Developer review recently published. Rather than picture it by itself, ARWR is provided here as a best-ranked alternative.

These market pros have insights you and I can't have because their everyday job is to satisfy investment organizations running billion-dollar portfolios who want to adjust their holdings in multi-million-dollar trade transactions. These market-makers [MMs] have to round up sellers when their clients want to buy, and buyers when they want to sell. That's hard to do when most investors will hold off to get better prices, whether they are buying or selling.

And when lots of money is involved in each trade, the players get pretty careful about what they want to do and when they will do it. But the big-money types work hard to be on top of developments, following some issues intently, anticipating what is likely to be happening to stock prices in the near future. Depending on what they know, or think they know, and what they think others believe is likely to happen, they may take surprising postures. Often their holding-period horizons are months, not years. Or even less.

So, the MMs have to respond when a big-money house says "sell a bunch of this and buy a lot of that, and do it in the next 15 minutes, or you can forget about keeping us as a good repeat-order client".

The MMs will round up any of their other clients who they know have holdings in the stocks or appetites (at a price) to initiate, expand or contract holdings in the issues involved. It's rare when a "cross" can be made with enough "other side of the trade" exists at acceptable prices to "fill" the trade order without having to put some of their own firm's capital at risk in order to balance buying demand with selling supply.

As market-makers, they will provide the balancing position when they can set up a hedge deal to protect the market risk involved in their "facilitation" of the trade's being completed. If they can't, then the trade order gets killed, not filled, to wait for a time when the market is more accommodating.

But what it takes to buy that market risk price-change protection for the MM tells what the players on both sides of the "insurance" market believe can happen to the stock's price during the limited lives of the derivative contracts for options, futures, swaps, or other highly leveraged involved instruments used in the hedge.

That's where we find the balances between forecast upside price gain prospects and price drawdown exposures today and can compare them with what has been seen day by day over the past couple of decades. That is what supports the opening statements above about +15% to +30% gains in specific stocks. Those are fact-based histories of all prior real-market experiences from forecasts made before the fact, not just blown smoke over some after-the-fact single illustration of convenient history.

"Sarepta Therapeutics, Inc. focuses on the discovery and development of RNA-based therapeutics, gene therapy, and other genetic medicine approaches for the treatment of rare diseases. The company offers EXONDYS 51, a disease-modifying therapy for Duchenne muscular dystrophy (DMD). Its products pipeline include Golodirsen, a product candidate that binds to exon 53 of dystrophin pre-mRNA, which results in exclusion or skipping of exon during mRNA processing in patients with genetic mutations; and Casimersen, a product candidate that uses phosphorodiamidate morpholino oligomer [PMO] chemistry and exon-skipping technology to skip exon 45 of the DMD gene. In addition, the company's pipeline comprises SRP-5051, a peptide conjugated PMO that binds to exon 51 of dystrophin pre-mRNA. It has collaboration agreements with Nationwide Children's Hospital to advance micro-dystrophin gene therapy program under the research and license option agreement; Galgt2, a gene therapy program for the treatment of DMD; and Neutrophin 3, a gene therapy program to treat Charcot-Marie-Tooth neuropathies. The company also has a license agreement with Lysogene to develop LYS-SAF302, a gene therapy for mucopolysaccharidosis IIIA; a license and option agreement with Lacerta to develop treatments for CNS-targeted and lysosomal storage diseases; and research collaboration and option agreement with Genethon to develop micro-dystrophin gene therapy products. In addition, it has a research agreement with Duke University to advance gene editing CRISPR/Cas9 technology for restoring dystrophin expression; a collaboration agreement with Summit (Oxford) Ltd. to commercialize products in Summit's utrophin modulator pipeline; a strategic collaboration with Paragon Bioservices; and a strategic collaboration with CENTOGENE for the identification of patients with DMD in the Middle East and North Africa region. Sarepta Therapeutics, Inc. was founded in 1980 and is headquartered in Cambridge, Massachusetts."

Source: Yahoo Finance

SRPT's and ARWR's recent daily price ranges over the past 6 months are shown in Figures 1 and 2, along with measures of their current forecast price up-to-down balances. Also shown are the odds of long position gains being earned in the couple of months subsequent to points in time in the past 5 years when MMs had the same kind of outlook they have today.

Figure 1

source: Author

Figure 2

source: Author

As a contrast, here is what MM forecasts for the "market-index" ETF of SPDR S&P 500 Trust (SPY) looks like at this time:

Figure 3

source: Author

How effective the MMs have been in forecasting for these stocks is a matter of market records, when conditions of uncertainty similar to today's are examined. That was done in the row of data between the graphics of Figures 1-3. For ease of comparison, they are repeated and slightly expanded in Figure 4.

Figure 4

source: Author

As explained in the prior Biotech Developer revue featuring ARWR, the SRPT Range Index [RI] of 23 produced 108 of 124 net gain %Payoffs under TERMD of +30.1%.

A comparison of the +30.1% payoffs with the present forecast of +23.1% suggests an exceptional profit achievement with a degree of credibility for the current outlook of 1.30, as indicated at column [N] of Figure 4.

So much for the "good side" of a buy proposition; what about the "bad side"?

As we condition the credibility of the upside price change forecast by comparison with actual experience, so too do we look to see how bad the downside might get. But with concern only during those "long" holding periods when committed capital would be at risk under the TERMD discipline. All other periods are irrelevant, shocking as they may be.

Figure 1's data row tells what the worst case price drawdowns have been (an average of them) during all of each actual exposure period when they were to be held. What matters is how bad a fear of loss may get induced any time, not just whether or not it existed at the end of the holding. Investors will have varied reactions to the exposures, so there is no way to evaluate potential risk impact by historic outcomes. But some useful guidance may be provided by having knowledge of the maximum degree of intensity possibly becoming present.

One logically-simplified way to address the combination of stock price risk and reward is to weight each part by its probability and combine the two. The "Win Odds" of profitable position odds here for SRPT of 108 out of 124, or 87 out of 100 offer such a probability. One minus those odds, or 100 - 87 provides the loss probability weight. Thus 0.87 times +30.1% plus 0.13 times -8.7% produces a weighted net payoff of +25.1%.

To make this style of evaluation more comparable between varied investment opportunity situations, an integration of the likely holding periods used in the calculation is helpful. For SRPT, the average number of market days required by all 129 positions of the sample was only 40 out of the maximum 63 possible, because of the high proportion of upside target prices reached.

A standard evaluation measure used in many capital planning decision situations is the expected net payoff stated in "basis points" of 1/100ths 1%, per day of capital involvement. On a 365-day calendar year +19 bp/day when sustained for a year doubles the original capital, or a CAGR of +100%. When a smaller-count of 252 market days makes up a relevant year, the fewer days are each proportionally more powerful, so only 14 bp/mkt day does the 100% equivalent.

Comparison is the essence of evaluation. If the investing objective is to make capital as productive of future spend-able amounts as possible, using an odds-weighted bp/d yardstick can be helpful.

To that end, Figure 4 includes the relevant MM forecasts and their prior outcomes for ARWR and the market-index proxy of the SPDR S&P 500 Index ETF (SPY). Also, the average of some 2,700 current-day MM price-range forecast issues, and a ranked set of the day's likely 20 best of those near-term wealth-building stocks under TERMD portfolio discipline.

All of these comparisons in Figure 4 have the same basic data as included in the row of Figure 1 for SRPT. That is expanded by the columns [O] through [R] to provide for odds-weighted bp/day price-prospect evaluation comparisons.

Competition from the market-index alternative SPY at this point in time is rather limited because of an unenthusiastic upside target outlook of only +5.5% at a CAGR of only +9% and an Odds-Weighted net prospect [Q] of +0.8%. That is better, though, than the overall population of 2,711 where MM forecasts are a modest net decline (-2.2%).

Sarepta Therapeutics, Inc. and Arrowhead Pharmaceuticals Inc. both offer outstanding prospects for capital gains with strong odds for achievement in short periods of holding. SRPT has the larger potentials, but ARWR appears historically to have quicker achievement prospects. Payoff potentials in basis points per day are exceptional. For further information, please check my blog here on Seeking Alpha.

Disclosure: I/we have no positions in any stocks mentioned, but may initiate a long position in SRPT over the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Disclaimer: Peter Way and generations of the Way Family are long-term providers of perspective information, earlier helping professional investors and now individual investors, discriminate between wealth-building opportunities in individual stocks and ETFs. We do not manage money for others outside of the family but do provide pro bono consulting for a limited number of not-for-profit organizations.We firmly believe investors need to maintain skin in their game by actively initiating commitment choices of capital and time investments in their personal portfolios. So, our information presents for D-I-Y investor guidance what the arguably best-informed professional investors are thinking. Their insights, revealed through their own self-protective hedging actions, tell what they believe is most likely to happen to the prices of specific issues in coming weeks and months. Evidences of how such prior forecasts have worked out are routinely provided in the SA blog of my name.

Follow this link:
Sarepta Therapeutics, Inc. And Arrowhead Pharmaceuticals Now Top-Ranked Biotech Stock Buys - Seeking Alpha

A team of researchers in China have genetically engineered a pig with human DNA and transplanted skin grafts onto monkeys in a milestone they say will pave the way for future skin and organ transplantations.

In the United States alone, more than 113,000 people are awaiting organ transplants yet just over 36,000 occur each year, according to the Health Resources and Services Administration. Xenotransplantation, the process of grafting or transplanting organs or tissues between different species, may be a solution to the shortage of organs around the world and provide treatment for patients with terminal organ failure, write the researchers in bioRxiv, a pre-print server for biology that has not been certified by peer-review for publication in a journal.

Pigs are widely used in biomedical research yet they are not phylogenetically close to humans, so rejection and incompatibility can occur. Genetically modifying donor pigs to serve as a potential organ source may provide a potentially viable solution, but the necessary combinations of genetic modifications in pigs for human xenotransplantation have not yet been determined.

To test these parameters, researchers at the First Affiliated Hospital of Nanchang University in China removed key pig genes that trigger organ rejection and added eight human genes to modified pigs in order to further reduce the chance of an organ being rejected. Skin was then transplanted from the pigs to monkeys and survived up to 25 days without the monkeys requiring immunosuppressive drugs.

Genetic modification of the pig is necessary to account for the differences between the pig and human genome, especially from the immune and molecular compatibility aspects, write the authors, adding that CRISPR/Cas9 technology has accelerated this process but determining which combinations remains an open question.

The authors note that extensive genome editing in certain pig cells is not a practical endeavor because of the telomere length, which requires complex and extensive editing and a long cell culture time that may lead to cell aging or death. There is also a low risk that porcine endogenous retrovirus (PERV), a virus integrated into the genomes of pigs, could infect human hosts. Even so, the findings have great potential for clinical value to save severe and large area burn patients and other human organ failure.

As the skin is considered the vital, unique and immunogenicity organ, our preliminary success in skin xenotransplantation using the combination of multi-gene modified pig in NHP provides the approval of the concept, paves a way to initiate the other organ preclinical trial and clinical trial, implies a success of these organs xenotransplantation, writes study author Wang Gang in a comment, adding that genetically altered pigs may have the potential to become an unlimited organ source for future clinical transplantation.

The researchers add that their findings may also have applications for human disease modeling and potentially help to one day establish disease-resistant animals.

Originally posted here:
Pigs Genetically Engineered With Human Cells May Pave The Way For Future Skin Transplants - IFLScience

31 Jan 2020

Soccer players who repeatedly bonk their noggins against the ball have losses in episodic memory. The losses are subtle and likely unnoticeable. This subclinical effect is strongest in ApoE4 carriers, according to a study published January 27 in JAMA Neurology.

Researchers led by Michael Lipton of Albert Einstein College of Medicine in New York correlated the previous years heading exposure with memory scores. They questioned amateur players about their degree of heading, and found that people who were ApoE4-positive and regularly headed the ball had the worst delayed recall. Whether these memory blips signify a brewing subclinical pathology that could develop into neurodegenerative disease over time remains unclear, but Lipton said the findings suggest players might do best to at least tone down the number of headers they make in each game.

Multiple studies have linked participation in the military or in rough-and-tumble contact sports, such as American football, ice hockey, and boxing, to neuropsychological problems and subsequent neurodegenerative disease. However, evidence has also been mounting that that milder, subconcussive blows to the headsuch as those sustained during intentional heading of the ball by soccer playersalso take a cognitive toll and might even spark neurodegeneration (Matser et al., 2001;Feb 2017 news; Nov 2019 news).

Ouch! (And remember to buy milk.)

Little is known about how or if ApoE4, the strongest genetic risk factor for AD, influences cognitive consequences of these repetitive actions, although previous studies reported that American football players or boxers who inherited the ApoE4 allele were at greater risk of cognitive impairment than noncarriers (Jordan et al., 1997; Kutner et al., 2000).

First author Liane Hunter and colleagues investigated verbal memory loss experienced by amateur soccer players in the New York City area. Previously, the researchers had reported that the number of times a player headed the ball over a year correlated with poorer scores on tasks of verbal learning and memory (Levitch et al., 2018). Now, they factored ApoE genotype into the equation. The Einstein Soccer Study enrolled 379 participants who had been playing soccer regularly for more than five years. Of those, 355 were genotyped for ApoE. They answered a detailed computerized questionnaire, called HeadCount-12m, which incorporated information about the number of games or practices per month, months of play per year, and the average number of headers per game, to estimate the total number of headers over the prior year. They also underwent cognitive testing.

Three of the genotyped volunteers reported heading the ball more than 100,000 times over the past year, and were excluded as extreme outliers. The remaining 352 players averaged 23 years of age; 256 were men. Eighty-one carried at least one copy of ApoE4. The players headed the ball an average of more than 600 times, ranging from 70 to 3,800 headers over the year. The researchers split the volunteers into quartiles, with the lowest two considered low heading exposure, the third moderate, the fourth high. Players in the moderate and high exposure quartiles had lower scores on the CogState International Shopping List Delayed Recall (ISRL) test, a measure of verbal memory in which participants attempt to recall a 12-item shopping list 20 minutes after having it read to them. While players with low exposure recalled an average of 10 items, those in the moderate and high exposure groups recalled 9.3 and 9.2, respectively. The ISRL serves as an outcome measure in some Alzheimers clinical trials.

ApoE4 strengthened the association between heading and poor performance on the ISRL. Among carriers, the difference in ISRL scores between high- and low-frequency heading quartiles was fourfold greater than in noncarriers. When comparing scores in people with high versus moderate exposure, ApoE4 carriers had an 8.5-fold greater deficit than did noncarriers. ApoE4 seemed to amplify the differences between groups. Translated into absolute terms, noncarriers in the highest heading quartile scored 0.36 points lower on the ISRL than noncarriers with lowest heading exposure. For ApoE4 carriers, the most eager headers scored 1.49 points lower than those in the lowest quartile. Essentially, more frequent heading caused ApoE4 carriers to forget one more item on the shopping list than did noncarriers.

Lipton told Alzforum that this dip in memory is unlikely to be noticed in daily life. The mechanism behind it is unknown. The authors speculated that, as a carrier of lipids in the brain, ApoE could play a role in repairing damaged synapses following injury, and ApoE4 may do a subpar job. Lipton previously reported that high levels of soccer heading associated with microstructural damage to myelin, and considers it possible that ApoE could play a role in myelin repair (Lipton et al., 2013).

Henrik Zetterberg of the University of Gothenburg in Sweden noted that the effect on memory attributable to ApoE4 is small, and it is unclear how the allele would contribute to memory loss in response to injury at such a young age. He speculated that differences in the way microglia or astrocytes respond to injury in ApoE4 carriers could explain subtle changes in memory. He added that serum markers of axonal injury and neuroinflammationneurofilament light (NfL) and glial fibrillary acidic protein (GFAP)could connect pieces of the puzzle in future studies. Zetterberg previously reported elevated NfL in response to soccer heading (Wallace et al., 2018).

Zetterberg thinks the verbal memory dip by itself is unlikely to portend AD or other neurodegenerative diseases. To Lipton, that is the big question left open by the study. While forgetting the milk on the shopping list may not pose an issue now, could it signify a brewing subclinical pathology that could hasten neurodegeneration?

In an accompanying editorial, Sarah Banks of the University of California, San Diego, and Jesse Mez of Boston University School of Medicine emphasize that the data from this paper cannot answer this question: It should be stated explicitly that the intellectual jump from the current study findings to late-life cognitive decline and neurodegeneration, including chronic traumatic encephalopathy, is substantial.

These authors cautioned that the findings should not be used to enact policy changessuch as using ApoE screening to inform decisions about soccer play. Lipton thinks that, conceptually, using genetics to inform decisions about risk is no longer a stretch. Even without ApoE4 in the picture, reducing heading exposure among players who do it most frequently would be feasible, Lipton noted, given that the players with high heading exposure are a minority of players. Among this NYC cohort of amateurs, roughly a third of the players fell into the highest quartile of heading.Jessica Shugart

See original here:
Soccer Heading Has Greater Impact on Memory in ApoE4 Carriers - Alzforum

Researchers at KU Leuven have discovered that a defect in the ATP13A2 gene causes cell death by disrupting the cellular transport of polyamines. When this happens in the part of the brain that controls body movement, it can lead to Parkinsons disease.

With more than six million patients around the world, Parkinsons disease is one of the most common neurodegenerative disorders. Around twenty genetic defects have already been linked to the disease, but for several of these genes, we dont know what function they fulfill. The ATP13A2 gene used to be one of these genes, but researchers at KU Leuven have now discovered its function in the cell. The researchers explain how a defect in the gene can cause Parkinsons disease in their article ATP13A2 deficiency disrupts lysosomal polyamine export published in Nature.

We found that ATP13A2 transports polyamines and is crucial for their uptake into the cell, explains senior author Peter Vangheluwe, PhD, from the Laboratory of Cellular Transport Systems. Polyamines are essential molecules that support many cell functions and protect cells in stress conditions. But how polyamines are taken up and transported in human cells was still a mystery. Our study reveals that ATP13A2 plays a vital role in that process. Our experiments showed that polyamines enter the cell via lysosomes and that ATP13A2 transfers polyamines from the lysosome to the cell interior. This transport process is essential for lysosomes to function properly as the waste disposal system of the cell where obsolete cell material is broken down and recycled. However, mutations in the ATP13A2 gene disrupt this transport process, so that polyamines build up in lysosomes. As a result, the lysosomes swell and eventually burst, causing the cells to die. When this happens in the part of the brain that controls body movement, this process may trigger the motion problems and tremors related to Parkinsons disease.

Unraveling the role of ATP13A2 is an important step forward in Parkinsons research and sheds new light on what causes the disease, but a lot of work remains to be done.

Vangheluwe continues: We now have to investigate how deficient polyamine transport is linked to other defects in Parkinsons disease such as the accumulation of plaques in the brain and malfunctioning of the mitochondria, the energy factories of the cell. We need to examine how these mechanisms influence each other, he says. The discovery of the polyamine transport system in animals has implications beyond Parkinsons disease as well, because polyamine transporters also play a role in other age-related conditions, including cancer, cardiovascular diseases, and several neurological disorders. Now that we have unraveled the role of ATP13A2, we can start searching for molecules that influence its function. Our lab is already collaborating with the Centre for Drug Design and Discoverya tech transfer platform established by KU Leuven and the European Investment Fundand receives support from the Michael J. Fox Foundation.

Read this article:
Function of Gene Implicated in Parkinson's Disease Discovered - Clinical OMICs News

You wouldnt know that Lynda Marino has a serious heart condition, save for the scar that ends near the top of her breastbone.

Marino, 40, a busy mother of two young children, is tall, slender and outgoing and fortunate to be alive.

She was diagnosed in her mid-20s with cardiomyopathy, nearly died from cardiac arrest four years ago and weathered open-heart surgery on New Years Eve at the Cleveland Clinic.

Her sister, 35-year-old Marianne Potratz, has the condition that thickens and endangers heart muscle, too.

We don't look like the average people you might expect to have heart disease, Marino said.

The two sisters have become leading advocates for the Buffalo Niagara affiliate of the American Heart Association during the last few years, not so much because their condition is rare but because heart disease is so common.

They dont want themselves or you to become another statistic for the No. 1 killer in the nation.

Cardiovascular disease can take a life suddenly or over time, at any age. Those stricken young often have a genetic predisposition like Marino, who lives in East Amherst, or Potratz, of Grand Island, but the Heart Association estimates that 80 % of cases can be prevented with healthy living and decision-making.

You need to eat right, exercise regularly and talk with your primary care provider about your family history of heart disease. Health care visits and screenings are important as often as your provider recommends, said Dr. Vijay Iyer, chief of cardiovascular medicine in the University at BuffaloJacobs School of Medicine and Biomedical Sciences.

Nobody should get to the age of 25 without knowing their blood pressure and their cholesterol numbers, he said.

Action saves lives when it comes to heart disease

Ignorance is hardly bliss when it comes to heart disease, either.

High blood pressure and even diabetes, for example, often don't manifest themselves till theyve gone too far, said Iyer, who also directs structural heart interventions at Gates Vascular Institute and the complex valve clinic at Buffalo General Medical Center.

Most of the early symptoms can be very subtle or there may be no symptoms at all, he said. People could have had hypertension for a long time, and slowly built blockages in the arteries, and the first time they show up is in the hospital when theyve had a heart attack or had a stroke so not knowing about your physical condition, your medical history, can be quite deleterious. It can be potentially fatal.

Lynda Marino, left, and her sister, Marianne Potratz, right, walk with their mother, Susan Minbiole, near the house where they grew up in East Amherst. Genetic testing after Marino suffered a cardiac arrest in 2015 showed that the sisters and their father, Barry Minbiole, have a genetic mutation that predisposes them to cardiomyopathy, a heart condition that must be closely monitored. (Robert Kirkham/Buffalo News)

It can be easy to take health for granted, particularly when you lead a busy life.

Marino knows. She learned she had cardiomyopathy in 2006, while in her mid-20s, when she was diagnosed with pneumonia. Her primary physician ordered a chest X-ray that showed signs of the condition, which thickens the heart walls, hampers blood flow and sometimes damages valves.

Marino was encouraged to see her doctor regularly, limit her exercise to moderate levels and eat right. She also was urged to be mindful of dizziness or extreme fatigue two signs of disease progression.

In the years that followed, she felt fine. She and her husband, John, chief technical officer in the Cleveland Hill School District, started a family. She also landed a job as marketing director with Canterbury Woods retirement communities.

Things changed unexpectedly on Sept. 12, 2015, when Marino went into cardiac arrest while driving home from T.J. Maxx and Aldi in the Town of Lockport.

I had a newborn son at home, she said. I had a 2-year-old daughter. I worked full time. Who knows what I was feeling, or just ignoring, beforehand because life was so insane.

Her right foot slipped off the gas as she slumped past the steering wheel onto the console. The car crawled south on Transit Road at 5 mph, while her daughter, Claire, cried frantically in a car seat behind her.

Thats when the miracles started happening, she said, recounting what others since have told her.

Chris James, a fellow motorist, saw what was happening, stopped his car, ran to the side of Marinos Forester SUV and was able to open the door because it didnt have automatic locks. He directed the car to the side of the road, turned off the ignition and called 911.

Bill and Peggy Killewald watched the commotion across four lanes of traffic while Bill, a retired veterinarian, pumped gas at a NOCO station. The couple ran to Marino, whose electrical impulses to her heart had stopped.

When Bill was doing CPR, he said I had no pulse, she said. My lips were blue and he, as a doctor, thought I was gone.

A Niagara County sheriffs deputy armed with an automated external defibrillator next joined the life-saving effort. At the time, the department was one of few in regional law enforcement that equipped its patrol cars with AEDs. Had she driven a few miles south into her home county, her odds of survival would have been worse.

Rescue workers rushed her first to Lockport Memorial Hospital, then Buffalo General, where she spent four days in an induced coma to help her recuperate.

In the coming weeks, both she, her sister and parents were tested for a gene mutation that predisposes people to cardiomyopathy.

Both sisters already knew they had the condition, confirmed through echocardiograms years earlier. They now learned they had the mutation, along with their father, Barry, 68, a retired Praxair engineer.

Nobody should get to the age of 25 without knowing their blood pressure and their cholesterol numbers, says said Dr. Vijay Iyer, a cardiologist at Gates Vascular Institute and Buffalo General Medical Center, as well as chief of cardiovascular medicine in the University at Buffalo Jacobs School of Medicine and Biomedical Sciences. (John Hickey/News file photo)

Several weeks later, surgeons at Buffalo General implanted defibrillators and pacemakers into Marino and Potratz, who have since called themselves the Sling Sisters because they needed to wear left arm supports for six weeks as they recovered.

The regional American Heart Association affiliate offered them support along the way, which is why they now share their stories as part of the Go Red for Women campaign, which encourages women to know their cardiovascular risks and take action to reduce them.

They were discouraged from eating too much salt, fatty meat and processed foods, running marathons or lifting heavy weights. They were encouraged to walk for exercise, eat more fruits, vegetables and seafood, and drink plenty of water.

Heart Association staff also encouraged the sisters to know their health screening numbers, particularly blood pressure, cholesterol, blood sugar, weight, and any sudden increases in fluid retention.

Both women also were put on beta blocker drugs to help regulate their heart rhythms.

We live very normal lives, Marino said, or at least I did for a couple of years.

She and her sister returned from a trip to Iceland and Paris in late 2018 and Marino began to experience more dizziness, shortness of breath and chest pressure when exerting herself. She led a nearly yearlong effort to find the best solution to removing substantial muscle scarring on her heart, and secure health insurance approval.

On New Years Eve, a cardiomyopathy team at the Cleveland Clinic performed an extensive myomectomy, slicing nearly a half ounce of damaged muscle from Marinos heart nearly twice as much as generally creates urgency for such open-heartsurgery.

Before this procedure was perfected, the only alternative was a heart transplant, said the sisters' mother, Susan Minbiole.

From left, Lynda Marino, Susan Minbiole and Marianne Potratz have become key supporters of the Go Red for Women campaign, which encourages women to know their cardiovascular risks and take action to reduce them. (Robert Kirkham/Buffalo News)

Marino hasnt been able to drive or lift anything heavier than a milk carton since her surgery. She has returned to the Cleveland Clinic twice since surgery and will do so less often going forward. She also continues to work with cardiologists and electrophysiologists in Buffalo.

The Minbiole family always has been tight. Marino lives just a few blocks from her parents, while Potratz and her husband, Seth, also are regulars at family gatherings that have taken on greater meaning in recent years. Family members vacation together more regularly, and their gratitude and giving has taken on greater proportions.

Friends and family members became part of the Sling Sisters team that has become a force in regional Heart Association fundraisers.

The experience also helped underline the importance of family, community and preparedness when it comes to good health.

We really promote hands-only CPR because my life was saved in part by bystanders, complete strangers, that jumped in to help me, Marino said. You could be someone else's hero by learning CPR or suggesting your friend go see the doctor because you're hearing her complain about an ache in her arm or other symptoms of heart disease.

The sisters are CPR-trained and, because there is little research on cardiomyopathy, Marino has enrolled in a Yale University study on exercise for those with the condition.

Meanwhile, they and their families marvel at medical advances that help Marino and Potratz stay on top of their challenges.

Marino has a device similar to an Apple Watch that can take an EKG, and both sisters have another device, half the size of a toaster, that takes heart readings from their pacemakers and defibrillators and transmit them by cell signal to health specialists in the event of an unusual reading.

The pacemaker and defibrillator will always be there to protect against any future cardiac arrest, Marino said. It doesn't stop it from happening, but it would stop it from killing me.

They hope more advances will come in the future and work toward that end in part because Marinos now 6-year-old daughter and 4-year-old son, Logan, also have the MYBPC3 gene mutation that predisposes them to the same condition.

As is the case for everyone, the sisters said, its better to know something like that than not.

Some say ignorance is bliss, Potratz said, but in my case, knowing that I'm protected is far more valuable than not having the information at all.

WNY's unhealthy habits could stunt economic growth, study says

See the rest here:
Two sisters, one near-death experience, and a warning about heart disease - Buffalo News

Genetically altering symbiotic gut bacteria in honey bees is successful at killing varroa mites, which tend to make bees sick and leave them at an increased risk of colony collapse disorder, according to a study published today (January 31) in Science.

Colony collapse disorder (CCD) occurs when the majority of a hive abandons ship, leaving behind the queen, honey and pollen stores, and young, immature bees behind. Without the workforce of a full hive, the colony fails. According to the US Department of Agriculture, there does not appear to be a single cause of CCD, rather, it is likely a combination of disease, parasites, poor nutrition, pesticide exposure, and other stressors on the hive.

One possible contributor to unhealthy hives are Varroa destructor mites, an invasive species that arrived in North America in the early 1980s. Not only do these parasites feed on the bees fat stores, but they also transmit a virus that leads to the deformation of their wings. As a bees health declines, it becomes more susceptible to contracting other illnesses. If a hive becomes infested with these mites, it might be enough of a threat for the healthy bees to bug out, leaving their hivemates behind.

To fight back against Varroa, researchers looked to Snodgrassella alvi, a symbiotic bacterium found within the gut of honey bees. Genetic modification of the microbes enabled them to destroy the mites from the inside out through RNA interference (RNAi). The engineered bacteria produced double-stranded RNA that induced the mites to launch an RNAi defense to destroy those sequences. Because the bacterial sequences matched those from the varroa genome critical to the mites survival, the silencing mechanism wiped out the mite transcripts as well, killing the parasites

It is a bit like a customized medicine for honey bees, Jeffrey Scott, an insect toxicologist at Cornell University who was not involved with the study, tells Science. Being able to engineer a gut microbe and specifically regulate gene expression in the host has enormous implications.

By using S. alvi as a manufacturer, the team was able to provide a continued supply of the RNA, providing a useful window for the bees to fight back against the mites. The effects lasted for the duration of the 15-day-long experiment and bees with the altered bacteria were 70 percent more likely to kill mites within 10 days than those without it.

If the technique works in the field, that could be the end of Varroa and the viruses, Robert Paxton, a bee ecologist at Martin Luther University who was not involved with the study, tells Science.

While the results of this small-scale experiment are encouraging, the method wont be used in the wild anytime soon. Releasing bacteria with gene-silencing potential invariably raises containment questions along with concerns that mutations may cause unintended consequences.

Youre turning off genes [via RNAi], honeybee epidemiologist Dennis vanEngelsdorp of the University of Maryland who was not involved with the study tells Science News. There has to be a very healthy debate about how do we regulate this?

Lisa Winter is the social media editor forThe Scientist. Email her at lwinter@the-scientist.com or connect on Twitter @Lisa831.

View post:
Engineered Microbe in Bees Guts Fends off Deadly Varroa Mite - The Scientist