A group led by researchers at Baylor College of Medicine has identified significant differences at the epigenetic level the chemical tags in DNA that help regulate gene expression between two clinically distinct forms of acute childhood malnutrition known as edematous severe acute malnutrition (ESAM) and non-edematous SAM (NESAM).

The researchers report in the journal Nature Communications that ESAM, but not NESAM, is characterized by a reduction in methyl chemical tags in DNA and complex changes in gene activity, including both enhanced and reduced gene expression. Some of the genes that lost their methyl tags have been linked to other disorders of nutrition and metabolism, such as abnormal blood sugar and fatty liver disease, conditions that also have been observed in ESAM. The findings support consideration of methyl-group supplementation in ESAM.

Severe acute childhood malnutrition presents in two clinically distinct forms: ESAM and NESAM, said corresponding author Dr. Neil Hanchard, assistant professor of molecular and human genetics and the USDA/ARS Children's Nutrition Research Center at Baylor. ESAM is characterized by body swelling and extensive dysfunction of multiple organs, including liver, blood cells and the gut, as well as skin and hair abnormalities. NESAM, on the other hand, typically presents with weight loss and wasting.

The differences between ESAM and NESAM are still not fully explained despite decades of studies addressing this question. In the current study, Hanchard and his colleagues looked to better understand the conditions by investigating whether there were differences at the molecular level, specifically on DNA methylation.

The decision to look at DNA methylation was partly driven by previous studies looking at biochemical markers in these individuals. In particular, the turnover of a particular amino acid called methionine, said Hanchard.

Previous work has shown that methionine turnover is slower in ESAM than in NESAM. Methionine is a central ingredient of 1-carbon metabolism, a metabolic pathway that is key to DNA methylation. Lower methionine turnover suggested the possibility of alterations in DNA methylation.

First, we conducted a genome-wide analysis of DNA methylation. When we found in children acutely ill with ESAM genes with levels of DNA methylation that were significantly different from those in NESAM patients, the levels were always lower. Of the genes analyzed, 161 showed a highly significant reduced level of methylation in ESAM, when compared to the same genes in NESAM, Hanchard said.

Interestingly, a group of adults who had recovered from having ESAM malnutrition in their childhood did not show the same reduction in DNA methylation the researchers observed in childhood acute cases. This suggested that lower DNA methylation was probably related to acute ESAM.

Knowing that DNA methylation helps regulate gene expression, Hanchard and his colleagues next investigated whether there were differences in gene expression between ESAM and NESAM. They found that reduced overall methylation in ESAM resulted in a complex pattern of gene expression changes. For some genes, having reduced methylation enhanced their expression, while for others it reduced it.

Among the genes that were highly affected by reduced methylation were some of those related to conditions such as blood sugar regulation, fatty liver disease and other metabolic problems, which are also commonly seen more often in ESAM than NESAM.

Our findings contribute to a better understanding of the molecular events that likely result in the differences between ESAM and NESAM, Hanchard said. Although we still dont know why malnutrition leads to ESAM in some children, while it results in NESAM in others, our findings suggest that, once ESAM gets on its way, methylation changes are likely involved in the clinical signs and symptoms of the condition. There is also evidence that individual genetic variation also influences the level of DNA methylation. Furthermore, I am excited about the possibility that altering the molecular outcome of malnutrition with specific interventions could one day help alter the clinical outcome.

Other contributors to this work include first author Katharina V. Schulze, Shanker Swaminathan, Sharon Howell, Aarti Jajoo, Natasha C. Lie, Orgen Brown, Roa Sadat, Nancy Hall, Liang Zhao, Kwesi Marshall, Thaddaeus May, Marvin E. Reid, Carolyn Taylor-Bryan, Xueqing Wang, John W. Belmont, Yongtao Guan, Mark J. Manary, Indi Trehan and Colin A. McKenzie.

See a complete list of author affiliations and financial support for this study.

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Form of severe malnutrition linked to DNA modification - Baylor College of Medicine News

RPC, Inc.s RES troubles seem to be never ending. The oilfield service provider, which has lost 51.4% of its value over the past year, is traversing rough waters amid several headwinds.The struggle is likely to continue as the companys prospects appear bleak, in view of lower expenditure from upstream companies.

The pricing chart shows that RPC has underperformed the ZacksOil And Gas - Field Servicesindustry, which has declined 29.4% in the past year.

Lets delve into the factors that have taken a toll on the firm.

Intensified competition in the domestic market has left limited room for oilfield services companies to charge premium prices for the services being offered. Moreover, slowdown of demand for pressure pumping services in shale plays mars RPCs prospects. This is evident from third-quarter 2019 results, wherein weakness stemmed from lower activity levels and pricing in the companys pressure pumping service business, which in turn affected the bottom line. Also, pressure pumping is likely to remain soft in North America. This business being RPCs biggest service line, the firms business outlook appears gloomy.

Explorers and producers are constrained by the reduction in capacity for borrowings and an increase in the cost of capital. Also, explorers are facing constant pressure from investors for higher returns instead of production growth. These headwinds are likely to lower investments by explorers and producers in the North American land market. Hence, conservative spending by customers is likely to hurt demand for the companys services.

Commodity prices will continue to remain in the bearish territory as demand for energy remains low, owing to a slowdown in global economic growth. Thus, explorers and producers are not getting enough incentives to produce hydrocarbon volumes in a massive scale. The drop in production volumes will likely keep demand for oilfield services low.

Industry Weakness

The Oil and Gas - Field Services industry currently has a Zacks Industry Rank of 239 out of 255 (Bottom 6%). As the industry is not expected to perform impressively in the coming days, the stock will likely underperform the market.

The above-mentioned factors are being reflected in the companys downward earnings estimate revisions.

Earnings Estimate Revisions

The Zacks Consensus Estimate for RPCs 2019 loss is pegged at 17 cents, which has witnessed no upward movement but 10 downside estimate revisions in the past 60 days. This suggests fall of 120.7% from the year-ago reported figure.

Given these headwinds, RPC seems a risky bet that investors should avoid at the moment. This is reflected in its Zacks Rank #5 (Strong Sell).

Stocks to Consider

Some better-ranked stocks in the energy sector include CNX Resources Corporation CNX, Antero Midstream Corporation AM and Frank's International N.V. FI, each carrying a Zacks Rank #2 (Buy). You can seethe complete list of todays Zacks #1 Rank (Strong Buy) stocks here.

CNX Resources earnings for the current year have witnessed four upward revisions in the past 60 days versus no movement in the opposite direction.

Antero Midstreams bottom line for the current quarter is expected to skyrocket 130% year over year.

Frank's Internationals bottom line for 2019 is expected to rise 23.8% year over year.

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Here's Why You Should Avoid Betting on RPC (RES) Stock Now - Nasdaq

A womans genetic background can powerfully modifiy her cancer risk from a BRCA1 mutation.

By Jocelyn KaiserDec. 17, 2019 , 4:00 PM

Women who learn that they have a mutation in the breast cancer gene BRCA1 face a wrenching decision. Their doctor or genetic counselor will likely tell them that women with such mutations have, on average, a 72% lifetime risk of breast cancer and a 44% risk of ovarian cancer. Given that, up to half decide to have prophylactic mastectomies, and many have ovaries removed, too.

But recent studies show a woman could receive a more individualized, accurate cancer risk estimate by factoring in other gene variants. A preprint posted last month finds that a person's "polygenic" background influences not only the disease risk conferred by a BRCA1 defect, but also risks from single gene mutations linked to colorectal cancer and heart disease. Some individuals were very likely to develop cancer or heart disease by age 75, the analysis showed, whereas in others the risk was not much greater than in a person without the high-risk mutation.

"It's pretty striking," says cardiologist and geneticist Amit Khera of Massachusetts General Hospital (MGH) in Boston, leader of the study, which is on the medRxiv preprint server. "It's become clear that there are both monogenic and polygenic [disease] drivers. The future is to assess both."

"The message is a very important one for patients and clinicians," says Teri Manolio of the National Human Genome Research Institute in Bethesda, Maryland. "Carriers of BRCA1 mutations or other pathogenic variants don't invariably develop disease, and genomics can be used to help parse carriers who are at lower risk." Others caution, however, that risk scores summing how dozens to thousands of other genetic variants interact with a single major disease gene aren't yet accurate enough to use in the clinic. The new paper "is teasing at the possibility, but there's a lot of work to be done," says Harvard University epidemiologist Peter Kraft.

MGH cardiology fellow Akl Fahed and others in Khera's group explored polygenic influences on the three important single-gene disorders in the United States: familial hypercholesterolemia, which leads to sky-high cholesterol levels and dramatically elevates risk of heart disease; Lynch syndrome, a flaw in DNA repair that brings a lifetime risk of colorectal cancer of about 60%; and inherited breast cancer, caused by variants in BRCA1 or BRCA2. They took advantage of databases that combine medical and genomic information from thousands of people, enabling researchers to tally how the many genetic variants with subtle effects modify disease risks and complex traits such as height.

Drawing on some 50,000 participants in the UK Biobank and 19,000 women tested for BRCA genes by the company Color Genomics, the team found that polygenic background strongly modified the risk of carrying a mutation in the key genes for the three disorders. For a small proportion of major disease gene carriers, other genetic variants boosted their overall risk of cancer or heart disease to about 80%, well above the average of 30% to 40% that Khera's group estimated for its study populations based on just the single disease gene mutations. (The team's monogenic disease risk predictions are lower than many other estimates for several possible reasons, Khera notes, including that the UK Biobank participants are healthier than the general population.) At the other extreme, the polygenic analysis suggested that a few people with those mutations have much lower risks than predicted by their single mutation alone, as low as 11% for colon cancer, 13% for breast cancer, and 17% for heart diseasenot much higher than other people in general.

Khera's group says adding polygenic data to single-gene tests could help people decide whether to take aggressive steps to head off diseasemastectomy or removal of the ovaries for women carrying BRCA mutations or frequent colonoscopies for people with Lynch syndrome. But the new study does not include enough data for clinical decisions, says genetic epidemiologist Antonis Antoniou of the University of Cambridge in the United Kingdom. Only 116 women in the UK Biobank sample had BRCA mutations, which he notes "is an extremely small number to make inferences about risks."

Two years ago, Antoniou led a study that reported on how polygenic scores influence risks in 25,000 carriers of BRCA mutations and found nearly as wide a range of overall cancer risks. His team has incorporated those data into a breast cancer risk estimator along with factors such as family history.

The MGH study is "an important and exciting paper" that complements other work, says David Ledbetter, chief scientific officer for the Geisinger Health System in Danville, Pennsylvania. His team recently looked at 92,000 participants in an ongoing genomic medicine study called MyCode, focusing on those who carried mutations predisposing them to 11 rare disorders that affect traits such as height, weight, and cholesterol levels. Incorporating polygenic scores helped predict those traits, the group reported on 25 October in Nature Communications.

It may be a while before physicians are comfortable telling patients how genetic backgrounds modify the risk posed by a major disease gene mutation. But some companies already offer polygenic scores for cancer and other diseases, and tests that combine both kinds of information are imminent. Before insurance companies agree to pay for such tests, Ledbetter cautions, "They're going to want to see much more clinical validation"including for minorities, because current polygenic analyses draw on data primarily from people of European ancestry.

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'Polygenic' profile could better predict disease risk for those with cancer mutations - Science Magazine

UNC Police is asking the public for help in their investigation of a series of credit card thefts fromdifferent medical research buildings on south campus earlier this month.

The department tweeted out photos on Tuesday morning, asking for helping identifying two people of interest in relation to the investigation.

According to an Alert Carolina post made on December 5, the thefts occurred during business hours on Wednesday December 4 inMacNider Hall, Beard Hall, the Bioinformatics Building and the Genetic Medicine Research Building among others. The post says credit cards were taken from unsecured offices and cubicles throughout the buildings.

Anyone seeing any suspicious activity anywhere on campus is reminded to call 911 immediately. UNC Police also encourage people to use smart security practices while in a work environment, like putting away visible valuables, keeping a record of all keys that have been issued and no admitting strangers into places of work.

If you have any information about the individuals, call the UNC Police Department at (919) 962-8100.

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UNC Police Investigating Series of Credit Card Thefts on South Campus - Chapelboro.com

Three investigative therapies by Proteostasis Therapeutics PTI-801, PTI-808, and PTI-428 showed potential to treat cystic fibrosis (CF) patients ineligible for approved CFTR modulators after patient-specific lab models produced promising results that support a future clinical trial.

Funded by the EUs initiative HIT-CF (Human Individualized Therapy of CF), this early study was conducted on patient organoids, which are miniaturized organ models derived from patient cells.

Based on the positive results, a clinical trial in adult CF patients is expected to start in 2020. If successful, the trial results may serve as the basis for a marketing authorization applicationin Europe in 2021.

With the help of CF-Europe (a patient organization) and the European Cystic Fibrosis Society Clinical Trial Network (ECFS-CTN), HIT-CF has been recruiting adult CF patients to collect tissue samples and create organoids, three-dimensional organ models grown in the lab.

Organoids mimic several characteristics of the organ from which they are derived, and are genetically identical to the donor. As such, they allow researchers to study biological processes and response to treatments in an environment that closely resembles human organs. As organoids are basically human cells cultured outside the body, they are said to be ex-vivo models.

The idea is to screen treatment candidates in the lab using intestinal organoids, or mini-intestines, obtained from rectal tissue (biopsies) of patients, which are collected through a quick and painless procedure. Then, based on how the organoids respond to each therapeutic candidate, a group of patients will be selected to enroll in a clinical trial.

Because the organoids can help determine the therapeutic candidate most likely to give the best results, researchers can personalize treatments for each patient before starting the trial.

So far, intestinal organoids from more than 300 patients have been created, of which 65 have been used to test Proteostasis potential CFTR modulators.

Proteostasis is honored to have been invited to participate in the HIT-CF project, and is the only company in the group with a combination of novel CFTR modulators being testedex-vivo. We are very enthusiastic about the progress of the study, Geoffrey Gilmartin, MD, chief medical officer of Proteostasis, said in a press release.

The positive results obtained on organoids support the launch of a clinical trial called CHOICES Crossover trial based on HumanOrganoidIndividual response inCF EfficacyStudy that will test the potential treatments on patients whose organoids responded favorably to the agents.

The study will also evaluate if organoids are good models to identify promising CF therapies, that is, if the responses measured on organoids translate to potential clinical benefits in patients, as reflected by lung function tests (FEV1) or sweat tests.

CHOICES will be a placebo-controlled, double-blind study that includes an eight-week treatment period, plus six months of constant dosing.

The study includes Proteostasis three candidate CFTR modulators, specially intended for patients who carry rarer CFTR genetic defects. All three compounds have different modes of action. PTI-801 works as a CFTR corrector, PTI-808 is a CFTR potentiator, and PTI-428 is a CFTR amplifier.

The trial is planned to start in mid-2020, with its first data anticipated for the end of 2020.

If moving forward, CHOICES will become the first trial based on personalized medicine for CF patients.

The inequality in access to CFTR modulators is an acute problem across Europe where 1 in 5 individuals do not have a F508del mutation [the most common CF-causing mutation]. In addition, drug reimbursement policies are leading to an ever-growing gap between patients who do, and those who do not have effective treatment options, said Christiane De Boeck, Work Package Leader at HIT-CF.

At HIT-CF Europe, we believe that novel strategies such as personalized medicine and development of new treatment options are central to addressing the inequality of access across the continent. We are thrilled with these initial results and look forward to providing additional updates, De Boeck added.

Gilmartin said that in Europe more than 2,300 adult CF patients are ineligible for approved CFTR modulators, and therefore excluded from participating in clinical trials.

This projects proposed personalized medicine approach is paving a potential new way to develop and provide access to novel CFTR modulators for patients with the most dire need for treatment options that target the cause of the disease. Additionally, based on an individual patients disease phenotype, and not just the genetic designation, this approach could also create a new path towards more effective treatment for all people with CF, Gilmartin said.

Proteostasis is also running a clinical trial evaluating a combination of the three candidate therapies for the treatment of CF patients who have at least one copy of the F508del mutation in the CFTR gene.

Ana is a molecular biologist enthusiastic about innovation and communication. In her role as a science writer she wishes to bring the advances in medical science and technology closer to the public, particularly to those most in need of them. Ana holds a PhD in Biomedical Sciences from the University of Lisbon, Portugal, where she focused her research on molecular biology, epigenetics and infectious diseases.

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Patrcia holds her PhD in Medical Microbiology and Infectious Diseases from the Leiden University Medical Center in Leiden, The Netherlands. She has studied Applied Biology at Universidade do Minho and was a postdoctoral research fellow at Instituto de Medicina Molecular in Lisbon, Portugal. Her work has been focused on molecular genetic traits of infectious agents such as viruses and parasites.

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Personalized CF Medicine to be Tested for Rare Genetic Defects in Europe - Cystic Fibrosis News Today

Elmwood Park, NJ, Dec. 19, 2019 (GLOBE NEWSWIRE) -- BioReference Laboratories, Inc., an OPKO Health Company, along with its genetics and genomics laboratory, GeneDx, Inc., and oncology, urology and womens health division, GenPath Diagnostics, are pleased to provide a 2019 business update, highlighting new tests that lead to faster diagnoses, payer relationships that provide greater access to care, and new tools that empower patients to take responsibility of their health. Work completed by the company this year reinforces its commitment to healthcare providers, patients and payers, as well as the local community and its employees.

The healthcare industry is moving towards preventive, convenient and personalized care, and the landscape is shifting to place patients at the forefront of decisions regarding their health. As we nod to our history as a physician-led laboratory, we focused 2019 on strengthening our resources and making strategic investments that reinforce our commitment to providers and patients alike. As we celebrate this years accomplishments and look to the future, well continue striving to empower consumers with the knowledge and tools to drive their healthcare in the most simple, accurate and efficient manner, said Jon R. Cohen, M.D., Executive Chairman of BioReference Laboratories.

2019 Highlights Include:

About BioReference Laboratories, Inc.

BioReference provides comprehensive testing to physicians, clinics, hospitals, employers, government units, correctional institutions and medical groups. The company is in network with the five largest health plans in the United States, operates a network of 10 laboratory locations, and is backed by a medical staff of more than 160 MD, PhD and other professional level clinicians and scientists. With a leading position in the areas of genetics, womens health, maternal fetal medicine, oncology and urology, BioReference and its specialty laboratories, GenPath and GeneDx, are advancing the course of modern medicine. For more information, visithttps://www.bioreference.com.

About OPKO Health, Inc.

OPKO Health is a diversified healthcare company. In diagnostics, its BioReference Laboratories is one of the nation's largest full-service clinical laboratories; GeneDx is a rapidly growing genetic testing business; the 4Kscore prostate cancer test is used to assess a patients individual risk for aggressive prostate cancer following an elevated PSA and to help decide about next steps such as prostate biopsy; Claros 1 is a point-of-care diagnostics platform with a total PSA test approved by the FDA. In our pharmaceutical pipeline, RAYALDEE is our first pharmaceutical product to be marketed. OPK88003, a once-weekly oxyntomodulin for type 2 diabetes and obesity reported positive data from a Phase 2 clinical trial. Its among a new class of GLP-1/glucagon receptor dual agonists. OPK88004, a SARM (selective androgen receptor modulator) is currently being studied for various potential indications. The companys most advanced product utilizing its CTP technology, a once-weekly human growth hormone for injection, successfully met its primary endpoint and key secondary endpoints in a Phase 3 study and is partnered with Pfizer. OPKO also has research, development, production and distribution facilities abroad. More information is available at http://www.opko.com

Cautionary Statement Regarding Forward-Looking Statements

This press release contains "forward-looking statements," as that term is defined under the Private Securities Litigation Reform Act of 1995 (PSLRA), which statements may be identified by words such as "expects," "plans," "projects," "will," "may," "anticipates," "believes," "should," "intends," "estimates," and other words of similar meaning, including statements regarding our ability to improve access to the 4Kscore test, whether the 4Kscore test accurately determines a mans risk of aggressive prostate cancer, whether other diagnostic tests we develop lead to fewer missed detections, faster diagnosis and more accurate treatment of various disorders, or achieve other benefits, as well as other non-historical statements about our expectations, beliefs or intentions regarding our business, technologies and products, financial condition, strategies or prospects. Many factors could cause our actual activities or results to differ materially from the activities and results anticipated in forward-looking statements. These factors include those described in the OPKO Health, Inc. Annual Reports on Form 10-K filed and to be filed with the Securities and Exchange Commission and in its other filings with the Securities and Exchange Commission. In addition, forward-looking statements may also be adversely affected by general market factors, competitive product development, product availability, federal and state regulations and legislation, the regulatory process for new products and indications, manufacturing issues that may arise, patent positions and litigation, among other factors. The forward-looking statements contained in this press release speak only as of the date the statements were made, and we do not undertake any obligation to update forward-looking statements. We intend that all forward-looking statements be subject to the safe-harbor provisions of the PSLRA.

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BioReference Laboratories Showcases 2019 Growth through the Addition of Cutting Edge Tests, Greater Access to Services, and Optimized Patient...

Investors focused on the Finance space have likely heard of Innovative Industrial Properties (IIPR), but is the stock performing well in comparison to the rest of its sector peers? By taking a look at the stock's year-to-date performance in comparison to its Finance peers, we might be able to answer that question.

Innovative Industrial Properties is a member of the Finance sector. This group includes 839 individual stocks and currently holds a Zacks Sector Rank of #8. The Zacks Sector Rank includes 16 different groups and is listed in order from best to worst in terms of the average Zacks Rank of the individual companies within each of these sectors.

The Zacks Rank emphasizes earnings estimates and estimate revisions to find stocks with improving earnings outlooks. This system has a long record of success, and these stocks tend to be on track to beat the market over the next one to three months. IIPR is currently sporting a Zacks Rank of #1 (Strong Buy).

Over the past 90 days, the Zacks Consensus Estimate for IIPR's full-year earnings has moved 3.49% higher. This is a sign of improving analyst sentiment and a positive earnings outlook trend.

Based on the latest available data, IIPR has gained about 61.78% so far this year. Meanwhile, the Finance sector has returned an average of 20.19% on a year-to-date basis. This shows that Innovative Industrial Properties is outperforming its peers so far this year.

To break things down more, IIPR belongs to the REIT and Equity Trust - Other industry, a group that includes 117 individual companies and currently sits at #89 in the Zacks Industry Rank. This group has gained an average of 22.46% so far this year, so IIPR is performing better in this area.

Going forward, investors interested in Finance stocks should continue to pay close attention to IIPR as it looks to continue its solid performance.

Innovative Industrial Properties, Inc. (IIPR): Free Stock Analysis Report

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The views and opinions expressed herein are the views and opinions of the author and do not necessarily reflect those of Nasdaq, Inc.

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Has Innovative Industrial Properties (IIPR) Outpaced Other Finance Stocks This Year? - Nasdaq

The idea for gene therapya type of DNA-based medicine that inserts a healthy gene into cells to replace a mutated, disease-causing variantwas first published in 1972. After decades of disputed results, treatment failures and some deaths in experimental trials, the first gene therapy drug, for a type of skin cancer, was approved in China in 2003. The rest of the world was not easily convinced of the benefits, however, and it was not until 2017 that the U.S. approved one of these medicines. Since then, the pace of approvals has accelerated quickly. At least nine gene therapies have been approved for certain kinds of cancer, some viral infections and a few inherited disorders. A related drug type interferes with faulty genes by using stretches of DNA or RNA to hinder their workings. After nearly half a century, the concept of genetic medicine has become a reality.

These treatments use a harmless virus to carry a good gene into cells, where the virus inserts it into the existing genome, canceling the effects of harmful mutations in another gene.

GENDICINE:Chinas regulatory agency approved the worlds first commercially available gene therapy in 2003 to treat head and neck squamous cell carcinoma, a form of skin cancer. Gendicine is a virus engineered to carry a gene that has instructions for making a tumor-fighting protein. The virus introduces the gene into tumor cells, causing them to increase the expression of tumor-suppressing genes and immune response factors.The drug is still awaiting FDA approval.

GLYBERA:The first gene therapy to be approved in the European Union treated lipoprotein lipase deficiency (LPLD), a rare inherited disorder that can cause severe pancreatitis. The drug inserted the gene for lipoprotein lipase into muscle cells. But because LPLD occurs in so few patients, the drug was unprofitable. By 2017 its manufacturer declined to renew its marketing authorization; Glybera is no longer on the market.

IMLYGIC:The drug was approved in China, the U.S. and the E.U. to treat melanoma in patients who have recurring skin lesions following initial surgery. Imlygic is a modified genetic therapy inserted directly into tumors with a viral vector, where the gene replicates and produces a protein that stimulates an immune response to kill cancer cells.

KYMRIAH:Developed for patients with B cell lymphoblastic leukemia, a type of cancer that affects white blood cells in children and young adults, Kymriah was approved by the FDA in 2017 and the E.U. in 2018. It works by introducing a new gene into a patients own T cells that enables them to find and kill cancer cells.

LUXTURNA:The drug was approved by the FDA in 2017 and in the E.U. in 2018 to treat patients with a rare form of inherited blindness called biallelic RPE65 mutation-associated retinal dystrophy. The disease affects between 1,000 and 2,000 patients in the U.S. who have a mutation in both copies of a particular gene, RPE65. Luxturna delivers a normal copy of RPE65 to patients retinal cells, allowing them to make a protein necessary for converting light to electrical signals and restoring their vision.

STRIMVELIS:About 15 patients are diagnosed in Europe every year with severe immunodeficiency from a rare inherited condition called adenosine deaminase deficiency (ADA-SCID). These patients bodies cannot make the ADA enzyme, which is vital for healthy white blood cells. Strimvelis, approved in the E.U. in 2016, works by introducing the gene responsible for producing ADA into stem cells taken from the patients own marrow. The cells are then reintroduced into the patients bloodstream, where they are transported to the bone marrow and begin producing normal white blood cells that can produce ADA.

YESCARTA:Developed to treat a cancer called large B cell lymphoma, Yescarta was approved by the FDA in 2017 and in the E.U. in 2018. It is in clinical trials in China. Large B cell lymphoma affects white blood cells called lymphocytes. The treatment, part of an approach known as CAR-T cell therapy, uses a virus to insert a gene that codes for proteins called chimeric antigen receptors (CARs) into a patients T cells. When these cells are reintroduced into the patients body, the CARs allow them to attach to and kill cancer cells in the bloodstream.

ZOLGENSMA:In May 2019 the FDA approved Zolgensma for children younger than two years with spinal muscular atrophy, a neuromuscular disorder that affects about one in 10,000 people worldwide. It is one of the leading genetic causes of infant mortality. Zolgensma delivers a healthy copy of the human SMN gene to a patients motor neurons in a single treatment.

ZYNTEGLO:Granted approval in the E.U. in May 2019, Zynteglo treats a blood disorder called beta thalassemia that reduces a patients ability to produce hemoglobin, the protein in red blood cells that contains iron, leading to life-threatening anemia. The therapy has been approved for individuals 12 years and older who require regular blood transfusions. It employs a virus to introduce healthy copies of the gene for making hemoglobin into stem cells taken from the patient.The cells are then reintroduced into the bloodstream and transported to the bone marrow, where they begin producing healthy red blood cells that can manufacture hemoglobin.

This approach uses a synthetic strand of RNA or DNA (called an oligonucleotide) that, when introduced into a patients cell, can attach to a specific gene or its messenger molecules, effectively inactivating them. Some treatments use an antisense method, named for one DNA strand, and others rely on small interfering RNA strands, which stop instruction molecules that go from the gene to the cells protein factories.

DEFITELIO:This drug contains a mixture of single-strand oligonucleotides obtained from the intestinal mucosa of pigs. It was approved (with limitations) in the U.S. and the E.U. in 2017 to treat severe cases of veno-occlusive disease, a disorder in which the small veins of the liver become obstructed, in patients who have received a bone marrow transplant.

EXONDYS 51:In 2016 the FDA granted approval to Exondys 51 amid some controversy regarding its efficacy; two members of the FDA review panel resigned in protest of the decision. The therapy is designed to treat a form of Duchenne muscular dystrophy caused by mutations in the RNA that codes for the protein that helps to connect muscle fibers cytoskeletons to a surrounding matrix. Exondys 51 is effective in treating about 13 percent of the Duchenne population.

KYNAMRO:Approved by the FDA in in 2013, Kynamro is designed to inhibitor effectively shut down production ofa protein that helps to produce low-density lipoprotein (LDL). Injected subcutaneously, this therapy is used to lower LDL levels in patients who have dangerously high cholesterol.

MACUGEN:Age-related macular degeneration is the leading cause of vision loss in people age 60 and older. It is caused by deterioration of the center of the retina due to leaking blood vessels. Approved in the U.S., Macugen inhibits these blood vessels from growing under the retina, thus treating the disorder.

SPINRAZA:With its FDA approval in 2016, Spinraza became the first gene-based therapy for spinal muscular atrophy. The inherited disorder is caused by low levels of SMN, a key protein for the maintenance of motor neurons. Spinraza binds to RNA from a backup gene called SMN2, converting that RNA into instructions for making fully functioning SMN proteins.

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Gene Therapy Arrives - Scientific American

Jumana Y Al-Aama,1,2 Hadiah B Al Mahdi,1 Mohammed A Salama,1 Khadija H Bakur,1,2 Amani Alhozali,3 Hala H Mosli,3 Suhad M Bahijri,4 Ahmed Bahieldin,5,6 Lothar Willmitzer,7 Sherif Edris1,5,6

1King Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSA; 2King Abdulaziz University Faculty of Medicine, Department of Genetic Medicine, Jeddah, KSA; 3King Abdulaziz University, Faculty of Medicine, Department of Endocrinology and Metabolism, Jeddah, KSA; 4King Abdulaziz University, Faculty of Medicine, Department of Clinical Biochemistry, Jeddah, KSA; 5King Abdulaziz University, Faculty of Science, Biological Sciences Department, Jeddah, KSA; 6Ain Shams University, Department of Genetics, Cairo, Egypt; 7Max-Planck-Institut Fr Molekulare Pflanzenphysiologie, Molecular Physiology, Golm, DE, Germany

Correspondence: Sherif Edris; Jumana Y Al-AamaKing Abdulaziz University, Princess Al Jawhara Albrahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, KSATel +966 593 66 23 84Email seedris@kau.edu.sa; jalama@kau.edu.sa

Background: Type 2 diabetes, or T2D, is a metabolic disease that results in insulin resistance. In the present study, we hypothesize that metabolomic analysis in blood samples of T2D patients sharing the same ethnic background can recover new metabolic biomarkers and pathways that elucidate early diagnosis and predict the incidence of T2D.Methods: The study included 34 T2D patients and 33 healthy volunteers recruited between the years 2012 and 2013; the secondary metabolites were extracted from blood samples and analyzed using HPLC.Results: Principal coordinate analysis and hierarchical clustering patterns for the uncharacterized negatively and positively charged metabolites indicated that samples from healthy individuals and T2D patients were largely separated with only a few exceptions. The inspection of the top 10% secondary metabolites indicated an increase in fucose, tryptophan and choline levels in the T2D patients, while there was a reduction in carnitine, homoserine, allothreonine, serine and betaine as compared to healthy individuals. These metabolites participate mainly in three cross-talking pathways, namely glucagon signaling, glycine, serine and threonine and bile secretion. Reduced level of carnitine in T2D patients is known to participate in the impaired insulin-stimulated glucose utilization, while reduced betaine level in T2D patients is known as a common feature of this metabolic syndrome and can result in the reduced glycine production and the occurrence of insulin resistance. However, reduced levels of serine, homoserine and allothrionine, substrates for glycine production, indicate the depletion of glycine, thus possibly impair insulin sensitivity in T2D patients of the present study.Conclusion: We introduce serine, homoserine and allothrionine as new potential biomarkers of T2D.

Keywords: glucagon signaling, glycine production, bile secretion, insulin sensitivity/resistance

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

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Detection of Secondary Metabolites as Biomarkers for the Early Diagnos | DMSO - Dove Medical Press

Spark will continue its operations in Philadelphia as an independent company within the Roche GroupBasel, 17 December 2019 - Roche (SIX: RO, ROG; OTCQX: RHHBY) and Spark Therapeutics, Inc. (NASDAQ: ONCE) (Spark) today announced the completion of the acquisition following the receipt of regulatory approval from all government authorities required by the merger agreement.

Commenting on this important step forward, Severin Schwan, CEO of Roche, said, We are excited about this important milestone because we believe that together, Roche and Spark will be able to significantly improve the lives of patients through innovative gene therapies.This acquisition supports our long-lasting commitment to bringing transformational therapies and innovative approaches to people around the world with serious diseases.

Spark Therapeutics, based in Philadelphia, Pennsylvania, is a fully integrated, commercial company committed to discovering, developing and delivering gene therapies for genetic diseases, including blindness, haemophilia, lysosomal storage disorders and neurodegenerative diseases. Spark Therapeutics will continue to operate as an independent company within the Roche Group.

Today ushers in a new and promising era in the development of genetic medicines for patients and families living with inherited diseases and beyond, said Jeffrey D. Marrazzo, co-founder and CEO of Spark Therapeutics. Spark and Roche share an ethos of imagining the unimaginable. Together, we have the potential to change the future of medicine and deliver the medicines of tomorrow today. We couldnt be more thrilled about whats next.

About RocheRoche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve peoples lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the worlds largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.

Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. More than thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Moreover, for the eleventh consecutive year, Roche has been recognised as one of the most sustainable companies in the Pharmaceuticals Industry by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2018 employed about 94,000 people worldwide. In 2018, Roche invested CHF 11 billion in R&D and posted sales of CHF 56.8 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit http://www.roche.com.

About Spark TherapeuticsSpark Therapeutics is a fully integrated, commercial company committed to discovering, developing and delivering gene therapies. The company challenges the inevitability of genetic diseases, including blindness, haemophilia, lysosomal storage disorders and neurodegenerative diseases.

Founded in March 2013 as a result of the technology and know-how accumulated over two decades at Childrens Hospital of Philadelphia (CHOP), Spark Therapeutics investigational therapies have the potential to provide long-lasting effects, dramatically and positively changing the lives of patients with conditions where no, or only palliative, therapies exist. Greater understanding of the human genome and genetic abnormalities have allowed Spark Therapeutics scientists to tailor investigational therapies to patients suffering from very specific genetic diseases. This approach holds great promise in developing effective treatments to a host of inherited diseases.

Spark Therapeutics is headquartered in Philadelphia, Pennsylvania.

All trademarks used or mentioned in this release are protected by law.

CAUTIONARY STATEMENT REGARDING FORWARD-LOOKING STATEMENTS

SOME OF THE STATEMENTS CONTAINED IN THIS ANNOUNCEMENT ARE FORWARD-LOOKING STATEMENTS, INCLUDING STATEMENTS REGARDING, AMONG OTHER THINGS, THE EXPECTED CONSUMMATION OF THE TRANSACTION, WHICH INVOLVES A NUMBER OF RISKS AND UNCERTAINTIES, INCLUDING THE SATISFACTION OF CLOSING CONDITIONS FOR THE TRANSACTION, INCLUDING REGULATORY APPROVAL, THE TENDER OF A MAJORITY OF THE OUTSTANDING SHARES OF COMMON STOCK OF SPARK THERAPEUTICS, THE POSSIBILITY THAT THE TRANSACTION WILL NOT BE COMPLETED, AND OTHER RISKS AND UNCERTAINTIES DISCUSSED IN SPARK THERAPEUTICS PUBLIC FILINGS WITH THE UNITED STATES SECURITIES AND EXCHANGE COMMISSION (THE SEC), INCLUDING THE RISK FACTORS SECTIONS OF SPARK THERAPEUTICS ANNUAL REPORT ON FORM 10-K FOR THE YEAR ENDED DECEMBER 31, 2018, AND IN ANY SUBSEQUENT PERIODIC REPORTS ON FORM 10-Q AND FORM 8-K, AS WELL AS THE TENDER OFFER DOCUMENTS FILED BY ROCHE AND ITS ACQUISITION SUBSIDIARY AND THE SOLICITATION/RECOMMENDATION FILED BY SPARK THERAPEUTICS. THESE STATEMENTS ARE BASED ON CURRENT EXPECTATIONS, ASSUMPTIONS, ESTIMATES AND PROJECTIONS, AND INVOLVE KNOWN AND UNKNOWN RISKS, UNCERTAINTIES AND OTHER FACTORS THAT MAY CAUSE RESULTS, LEVELS OF ACTIVITY, PERFORMANCE OR ACHIEVEMENTS TO BE MATERIALLY DIFFERENT FROM ANY FUTURE STATEMENTS. THESE STATEMENTS ARE GENERALLY IDENTIFIED BY WORDS OR PHRASES SUCH AS BELIEVE, ANTICIPATE, EXPECT, INTEND, PLAN, WILL, MAY, SHOULD, ESTIMATE, PREDICT, POTENTIAL, CONTINUE OR THE NEGATIVE OF SUCH TERMS OR OTHER SIMILAR EXPRESSIONS. IF UNDERLYING ASSUMPTIONS PROVE INACCURATE OR UNKNOWN RISKS OR UNCERTAINTIES MATERIALIZE, ACTUAL RESULTS AND THE TIMING OF EVENTS MAY DIFFER MATERIALLY FROM THE RESULTS AND/OR TIMING DISCUSSED IN THE FORWARD-LOOKING STATEMENTS, AND YOU SHOULD NOT PLACE UNDUE RELIANCE ON THESE STATEMENTS. ROCHE AND SPARK THERAPEUTICS DISCLAIM ANY INTENT OR OBLIGATION TO UPDATE ANY FORWARD-LOOKING STATEMENTS AS A RESULT OF DEVELOPMENTS OCCURRING AFTER THE PERIOD COVERED BY THIS REPORT OR OTHERWISE.

Roche Group Media RelationsPhone: +41 61 688 8888 / e-mail: media.relations@roche.com- Nicolas Dunant (Head)- Patrick Barth- Daniel Grotzky- Karsten Kleine- Nathalie Meetz- Barbara von Schnurbein

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Roche concludes acquisition of Spark Therapeutics, Inc. to strengthen presence in gene therapy - GlobeNewswire

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Genetics just got personal. So boasted the website of 23andMe in 2008, just after launching its DNA testing service.

As we entered this decade, a small cohort of companies 23andMe, its Silicon Valley neighbor Navigenics, and Icelandic competitor deCODE Genetics were selling a future of personalized medicine: Patients would hold the keys to longer and healthier lives by understanding the risks written into their DNA and working with their doctors to reduce them.

We all carry this information, and if we bring it together and democratize it, we could really change health care, 23andMe cofounder Anne Wojcicki told Time magazine when it dubbed the companys DNA test 2008s invention of the year, beating out Elon Musks Tesla Roadster.

But in reality, the 2010s would be when genetics got social. As the decade comes to a close, few of us have discussed our genes with our doctors, but millions of us have uploaded our DNA profiles to online databases to fill in the details of our family trees, explore our ethnic roots, and find people who share overlapping sequences of DNA.

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Its become like Facebook for genes, driven by the same fundamental human desire to connect. And, as with Mark Zuckerbergs social media behemoth, this is the decade we reckoned with what it really means to hand over some of our most personal data in the process.

A 23andMe saliva collection kit for DNA testing.

It all panned out differently from the way I imagined in 2009, when I paid $985 to deCODE and $399 to 23andMe to put my DNA into the service of science journalism. (I spared my then-employer, New Scientist magazine, the $2,500 charge for the boutique service offered by Navigenics.)

I was intrigued by the potential of DNA testing for personalized medicine, but from the beginning, I was also concerned about privacy. I imagined a future in which people could steal our medical secrets by testing the DNA we leave lying around on discarded tissues and coffee cups. In 2009, a colleague and I showed that all it took to hack my genome in this way was a credit card, a private email account, a mailing address, and DNA testing companies willing to do business without asking questions.

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Much of the rest of what I wrote about DNA testing back then reflected pushback from leading geneticists who argued that the companies visions of personalized medicine werent ready for primetime.

As I explored the reports offered by 23andMe and deCODE, I couldnt help but agree especially when deCODE wrongly concluded that I carry two copies of a variant of a gene that would give me a 40% lifetime chance of developing Alzheimers. (Luckily, it wasnt cause for panic. Id pored over my DNA in enough detail by then to know that I carry only one copy, giving me a still-elevated but much less scary lifetime risk of about 13%.)

Despite such glitches, it still seemed that medicine was where the payoffs of mainstream genetic testing were going to be. As costs to sequence the entire genome plummeted, I expected gene-testing firms to switch from using gene chips that scan hundreds of thousands of genetic markers to new sequencing technology that would allow them to record all 3 billion letters of our DNA.

So in 2012, eager to provide our readers with a preview of what was to come, New Scientist paid $999 for me to have my exome sequenced in a pilot project offered by 23andMe. This is the 1.5% of the genome that is read to make proteins and is where the variants that affect our health are most likely to lurk.

Experts at the Medical College of Wisconsin in Milwaukee analyzed my exome. While they werent at that point able to tell me much of medical significance that I didnt already know, the article I wrote from the experience in 2013 predicted a future in which doctors would routinely scour their patients genomes for potential health problems and prescribe drugs that have been specifically designed to correct the biochemical pathways concerned.

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Im glad I included an important caveat: This may take several decades.

By then, the revolution promised by 23andMe and its competitors was faltering. Navigenics and deCODE had both been acquired by bigger companies and stopped selling DNA tests directly to the public.

23andMe, backed by the deep pockets of Google and other Silicon Valley investors, had enough cash to continue. But it fell foul of the FDA, which had decided that the company was selling medical devices that needed official approval to be put on the market. In a 2013 warning letter, the FDA said that 23andMe had failed to provide adequate evidence that its tests produced accurate results. By the end of 2013, 23andMe had stopped offering assessments of health risks to new customers.

Since then, the company has slowly clawed its way back into the business of health. In 2015, it was given FDA approval to tell customers whether they were carriers for a number of inherited diseases; in 2017, it started providing new customers with assessments of health risks once more.

I recently updated my 23andMe account, getting tested on the latest version of its chip. My results included reports on my genetic risk of experiencing 13 medical conditions. Back in 2013, there were more than 100 such reports, plus assessments of my likely responses to a couple dozen drugs.

In the lab, discovery has continued at a pace, but relatively few findings have found their way into the clinic.

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If youve recently been pregnant, you were probably offered blood tests to tell whether your fetus had a serious genetic abnormality. And if youve been diagnosed with cancer, a biopsy may have been sequenced to look for mutations that make some drugs a good bet and other ones a bust. Neither would have been common a decade ago.

But the wider health care revolution envisaged by Wojcicki remains far off.

A few weeks ago, I saw my doctor to discuss my moderately high blood cholesterol and had a conversation that Id once predicted would be common by now. I had signed up for a project called MyGeneRank, which took my 23andMe data and calculated my genetic risk of experiencing coronary artery disease based on 57 genetic markers, identified in a 2015 study involving more than 180,000 people.

My genetic risk turns out to be fairly low. After I pulled out my phone and showed my doctor the app detailing my results, we decided to hold off on taking a statin for now, while I make an effort to improve my diet and exercise more. But it was clear from her reaction that patients dont usually show up wanting to talk about their DNA.

We have all these naysayers and an immense body of research that is not being used to help patients, said Eric Topol, director of the Scripps Research Translational Institute in La Jolla, California, which runs the MyGeneRank project.

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Joseph James DeAngelo, the suspected "Golden State Killer," appears in court for his arraignment in Sacramento, April 27, 2018.

23andMes collision with the FDA wound up being a turning point in ways I didnt anticipate at the time. From the start, the company included an assessment of customers ancestries as part of the package. But after the FDA cracked down, it pivoted to make ancestry and finding genetic relatives its main focus. Offering the test at just $99, 23andMe went on a marketing blitz to expand its customer base competing with a new rival.

Ancestry.com launched its genome-scanning service in May 2012 and has since gone head-to-head with 23andMe through dueling TV ads and Black Friday discount deals.

DNA tests became an affordable stocking filler, as millions of customers were sold a journey of self-discovery and human connection. We were introduced to new genetic relatives. And we were told that the results might make us want to trade in our lederhosen for a kilt or connect us to distant African ancestors.

Today, Ancestrys database contains some 15 million DNA profiles; 23andMes more than 10 million. Family Tree DNA and MyHeritage, the two other main players, have about 3.5 million DNA profiles between them. And for the most dedicated family history enthusiasts, there is GEDmatch, where customers can upload DNA profiles from any of the main testing companies and look for potential relatives. It contains about 1.2 million DNA profiles.

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So far, so much fun. But DNA testing can reveal uncomfortable truths, too. Families have been torn apart by the discovery that the man they call Dad is not the biological father of his children. Home DNA tests can also be used to show that a relative is a rapist or a killer.

That possibility burst into the public consciousness in April 2018, with the arrest of Joseph James DeAngelo, alleged to be the Golden State Killer responsible for at least 13 killings and more than 50 rapes in the 1970s and 1980s. DeAngelo was finally tracked down after DNA left at the scene of a 1980 double murder was matched to people in GEDmatch who were the killer's third or fourth cousins. Through months of painstaking work, investigators working with the genealogist Barbara Rae-Venter built family trees that converged on DeAngelo.

Genealogists had long realized that databases like GEDmatch could be used in this way, but had been wary of working with law enforcement fearing that DNA test customers would object to the idea of cops searching their DNA profiles and rummaging around in their family trees.

But the Golden State Killers crimes were so heinous that the anticipated backlash initially failed to materialize. Indeed, a May 2018 survey of more than 1,500 US adults found that 80% backed police using public genealogy databases to solve violent crimes.

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I was very surprised with the Golden State Killer case how positive the reaction was across the board, CeCe Moore, a genealogist known for her appearances on TV, told BuzzFeed News a couple of months after DeAngelos arrest.

The new science of forensic genetic genealogy quickly became a burgeoning business, as a company in Virginia called Parabon NanoLabs, which already had access to more than 100 crime scene samples through its efforts to produce facial reconstructions from DNA, teamed up with Moore to work cold cases through genealogy.

Before long, Parabon and Moore were identifying suspected killers and rapists at the rate of about one a week. Intrigued, my editor and I decided to see how easy it would be to identify 10 BuzzFeed employees from their DNA profiles, mimicking Parabons methods. In the end, I found four through matches to their relatives DNA profiles and another two thanks to their distinctive ancestry. It was clear that genetic genealogy was already a powerful investigative tool and would only get more so as DNA databases continued to grow.

A backlash did come, however, after two developments revealed by BuzzFeed News in 2019. In January, Family Tree DNA disclosed that it had allowed the FBI to search its database for partial matches to crime-scene samples since the previous fall without telling its customers. I feel they have violated my trust, Leah Larkin, a genetic genealogist based in Livermore, California, told BuzzFeed News at the time.

Then, in May, BuzzFeed News reported that police in Centerville, Utah, had convinced Curtis Rogers, a retired Florida businessperson who cofounded GEDmatch, to breach the sites own terms and conditions, which were supposed to restrict law enforcement use to investigations of homicides or sexual assaults. That allowed Parabon to use matches in the database to identify the perpetrator of a violent assault.

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Larkin and other genealogists condemned the move, calling it the start of a slippery slope that would see the method being used to investigate more trivial crimes.

As barbs flew between genealogists working with law enforcement and those who advocate for genetic privacy, GEDmatch responded with new terms of service that extended the definition of violent crime, but also required users to explicitly opt in for their DNA profiles to be included in law enforcement searches.

Overnight, GEDmatch became useless for criminal investigations. Since then, the number of users opting in for matching to crime-scene samples has slowly increased, and now stands at more than 200,000. But progress in cracking criminal cases has remained slow.

Now that cops have seen the power of forensic genetic genealogy, however, they dont want to let it go. In November, the New York Times revealed that a detective in Florida had obtained a warrant to search the entirety of GEDmatch, regardless of opt-ins. It seems only a matter of time before someone tries to serve a warrant to search the huge databases of 23andMe or Ancestry, which dont give cops access sparking legal battles that could go all the way to the Supreme Court.

Genetic privacy, barely mentioned as millions of us signed up to connect with family across the world and dig into our ancestral roots, is suddenly front and center.

This week, Rogers and the other cofounder of GEDmatch, John Olson, removed themselves from the heat when they sold GEDmatch to Verogen, a company in San Diego that makes equipment to sequence crime-scene DNA. Verogen CEO Brett Williams told BuzzFeed News that he sees a business opportunity in charging police for access to the database but promised to respect users privacy. Were not going to force people to opt in, he said.

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But it isnt just whether cops can run searches against your DNA. 23andMe may not share your information with law enforcement, but customers are asked when they signed up whether if they are OK with their de-identified DNA being used for genetic research.

It might not be obvious when you fill in the consent form, but this lies at the heart of 23andMes business model. The reason the company pushed so hard to expand its database of DNA profiles is to use this data in research to develop new drugs, either by itself or by striking deals with pharmaceutical companies.

Ancestry has also asked its users to consent to participate in research, teaming up with partners that have included Calico, a Google spinoff researching ways to extend human lifespan.

You might be comfortable with all of this. You might not. You should definitely think about it because when the information is your own DNA, there really is no such thing as de-identified data.

That DNA profile is inextricably tied to your identity. It might be stripped of your name and decoupled from the credit card you used to pay for the test. But as 23andMe warns in its privacy policy: In the event of a data breach it is possible that your data could be associated with your identity, which could be used against your interests.

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And because you share a large part of your genome with close relatives, when you put your DNA profile into a companys database, you arent only making a decision for yourself: Their privacy is on the line, too.

Whether its due to concerns about privacy, a saturated market, or just that the novelty has worn off, sales of DNA ancestry tests are slowing. Ancestry has responded by offering a new product focused on health risks. Unlike 23andMe, it requires that tests are ordered through PWNHealth, a national network of doctors and genetic counselors.

Will this be the development that takes us back to the future I once imagined? Maybe so, but if the roller coaster of the past decade has taught me anything, its to be wary about making any predictions about our genetic future.

Peter Aldhous is a Science Reporter for BuzzFeed News and is based in San Francisco.

Contact Peter Aldhous at peter.aldhous@buzzfeed.com.

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10 Years Ago, DNA Tests Were The Future Of Medicine. Now Theyre A Social Network And A Data Privacy Mess. - BuzzFeed News

Clinicians should consider mosaic Angelman syndrome in the differential diagnosis of people who show milder symptoms of the disorder, a study suggests.

The study, Preserved expressive language as a phenotypic determinant of Mosaic Angelman Syndrome, was published in Molecular Genetics & Genomic Medicine.

Angelman syndrome (AS) is a genetic neurodevelopmental disorder usually associated with severe intellectual disability, difficulty speaking, loss of movement control (ataxia), and epileptic seizures. It is normally caused by the loss or malfunction of the maternal copy of the ubiquitin protein ligase E3A (UBE3A) gene in neurons from specific regions of the brain.

However, in some people, these genetic defects that affect the normal function of the UBE3A gene are only present in a handful of their cells. This phenomenon, known as mosaicism, can happen if one of the first cells of an embryo acquires a mutation in the UBE3A gene which is then passed on to their daughter cells as the embryo grows.

People with mosaic Angelman syndrome (mAS) typically have milder symptoms than those with Angelman syndrome. For instance, they experience milder expressive language delay with greater ability to attain meaningful words than typical Angelman patients.

In this study, researchers from the Vanderbilt University Medical Center and their collaborators set out to describe the clinical symptoms of mAS in a larger group of individuals to help clinicians with the differential diagnosis of Angelman syndrome.

The study included data from 22 people with mAS, whose caregivers filled out surveys at the medical center. Data from four additional patients was obtained from the Angelman Natural History Study, an observational study that followed the course of the disease in 302 Angelman patients over more than eight years. Clinical data from people with mAS was then compared to historical data from individuals with Angelman.

Findings revealed that nearly all mAS patients (90%) had some form of developmental delay. However, unlike those with Angelman, less than 15% of survey respondents said that mAS children showed signs of severe developmental delays before reaching the age of 1.

Compared with the significant language impairments seen in children with Angelman, 59% of the children with mAS retained the ability to articulate more than 20 words, with a fifth (20%) of them able to speak more than 1,000 words.

Other core features of Angelman, including ataxia, gait abnormalities, and limb tremulousness, were found in less than 33% of mAS children.

Additional clinical features of Angelman syndrome were also evident in patients with mAS: The three most prominent findings included abnormal sleep/wake cycles and decreased sleep in 73% of patients, followed by obesity in 64% of patients and heat sensitivity in 45% of patients, the researchers wrote. Constipation, a common problem in [Angelman syndrome] patients was also noted in the mAS cohort, with 72% of patients endorsing constipation.

Although children with mAS had milder speech impairments and were better able to engage in daily activities, they still faced many behavioral challenges that were typical in Angelman syndrome.

Anxiety was the most frequently endorsed behavior reported in our cohort, present to some degree in 95% of mAS patients and rated as severe in 43% of patients. Hyperactivity was commonly endorsed, reported in 59% of patients, the researchers wrote.

Overall these data encourage specialists to broaden the clinical features of [Angelman syndrome], said the researchers, who added that clinicians should consider tests to rule out mAS in individuals with developmental delay, hyperactivity, anxiety, and an uncharacteristically happy demeanor.

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

Total Posts: 11

Ana holds a PhD in Immunology from the University of Lisbon and worked as a postdoctoral researcher at Instituto de Medicina Molecular (iMM) in Lisbon, Portugal. She graduated with a BSc in Genetics from the University of Newcastle and received a Masters in Biomolecular Archaeology from the University of Manchester, England. After leaving the lab to pursue a career in Science Communication, she served as the Director of Science Communication at iMM.

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Mosaic Angelman Should Be in Differential Diagnosis of AS, Study Says - Angelman Syndrome News

CAMBRIDGE, Mass., Dec. 13, 2019 (GLOBE NEWSWIRE) -- Sarepta Therapeutics, Inc. (SRPT), the leader in precision genetic medicine for rare diseases, announced today that it has entered into an agreement with funds managed by Pharmakon Advisors, LP, that provides Sarepta with up to $500 million of borrowing capacity in two tranches. The first $250 million (Tranche A) is available shortly after closing in December 2019, with an additional $250 million (Tranche B) available at Sareptas option by Dec. 31, 2020, subject to certain conditions. Both tranches are available at a rate of 8.5% annually, payable quarterly. The facility will mature 48 months from the Tranche A closing date. Additional information on the agreement will be set forth in a Form 8-K to be filed by the Company with theSecurities and Exchange Commission.

Pharmakon Advisors, LP, is the investment manager of the BioPharma Credit funds including BioPharma Credit Investments V LP and BioPharma Credit PLC (BPCR.L), the only listed investor specialized in life sciences debt.

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

Forward-Looking StatementThis press release contains "forward-looking statements." Any statements contained in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Words such as "believes," "anticipates," "plans," "expects," "will," "intends," "potential," "possible" and similar expressions are intended to identify forward-looking statements. These forward-looking statements include statements regarding Sareptas ability to borrow funds under the agreement with Pharmakon Advisors, L.P., and the timing and terms of the borrowing; and Sareptas mission to profoundly improve and extend the lives of patients with rare genetic-based diseases.

These forward-looking statements involve risks and uncertainties, many of which are beyond Sarepta's control. Known risk factors include, among others, market conditions, Sareptas market capitalization, any refusal by Pharmakon Advisors, L.P. to fund and other Company factors or circumstances that could negatively impact Sareptas ability to satisfy its obligations or borrow under the terms of the agreement with Pharmakon Advisors, L.P. There can be no assurance that Sarepta will be able to comply with the terms of the agreement with Pharmakon Advisors, L.P., which may result in an event of default under such agreement that could give Pharmakon Advisors, L.P. the right to require immediate payment of any amounts borrowed under such agreement or to exercise its rights with respect to the assets of Sarepta that are collateral or have been pledged by Sarepta as security or other assets of Sarepta; Sarepta may not be able to execute on its business plans, including meeting its expected or planned regulatory milestones and timelines, research and clinical development plans, and bringing its product candidates to market, for various reasons, some of which may be outside of Sareptas control, including possible limitations of company financial and other resources, manufacturing limitations that may not be anticipated or resolved for in a timely manner, and regulatory, court or agency decisions, such as decisions by the United States Patent and Trademark Office with respect to patents that cover Sareptas product candidates; and those risks identified under the heading Risk Factors in Sareptas most recent Annual Report on Form 10-K for the year ended December 31, 2018 and most recent Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) as well as other SEC filings made by the Company which you are encouraged to review.

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

Internet Posting of Information

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

Source: Sarepta Therapeutics, Inc.

Sarepta Therapeutics, Inc.

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

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

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Sarepta Therapeutics Announces $250 Million of Non-Dilutive Senior Secured Loan Financing - Yahoo Finance

CAMBRIDGE, Mass.--(BUSINESS WIRE)--Triplet Therapeutics, Inc., a biotechnology company harnessing human genetics to develop treatments for repeat expansion disorders at their source, launched today with $59 million in financing including a $49 million Series A financing led by MPM Capital and Pfizer Ventures U.S. LLC, the venture capital arm of Pfizer Inc. (NYSE: PFE). Atlas Venture, which co-founded and seeded Triplet with a $10 million investment, also participated in the Series A alongside Invus, Partners Innovation Fund and Alexandria Venture Investments.

Triplet was founded in 2018 by Nessan Bermingham, Ph.D., a serial biotech entrepreneur and venture partner at Atlas Venture, along with Atlas Venture and Andrew Fraley, Ph.D., to pursue a transformative approach to developing treatments for repeat expansion disorders, a group of more than 40 known genetic diseases associated with expanded DNA nucleotide repeats. A significant body of human genetic evidence has identified that one central pathway, known as the DNA damage response (DDR) pathway, drives onset and progression of this group of disorders, which include Huntingtons disease, myotonic dystrophy and various spinocerebellar ataxias.

Triplet is developing antisense oligonucleotide (ASO) and small interfering RNA (siRNA) development candidates to precisely knock down key components of the DDR pathway that drive repeat expansion. This approach operates upstream of current approaches in development, targeting the fundamental driver of these diseases. By precisely reducing activity of select DDR targets, Triplets approach is designed to halt onset and progression across a wide range of repeat expansion disorders.

The company has a fully assembled senior management team of industry veterans. Nessan Bermingham, Ph.D., co-founder, president and chief executive officer, has nearly two decades of experience leading life science startups and is a co-founder of Intellia Therapeutics and Korro Bio. Irina Antonijevic, M.D., Ph.D., senior vice president of development, previously led translational medicine and early development at Wave Life Sciences. Brian Bettencourt, Ph.D., senior vice president of computational biology & statistics, comes to Triplet from Translate Bio, where he led modeling and design of oligonucleotide and mRNA therapeutics. David Morrissey, Ph.D., senior vice president of technology, formerly led technology development and delivery of CRISPR/Cas9 gene editing candidates at Intellia Therapeutics. Eric Sullivan, CPA, chief financial officer, brings experience leading financial operations at Gemini Therapeutics and bluebird bio. Jeffrey M. Cerio, Pharm.D., J.D., senior vice president & general counsel, served as senior corporate counsel at Moderna, Inc. before joining the Triplet team.

Were excited to launch Triplet today to transform the treatment of repeat expansion disorders, Dr. Bermingham said. This milestone would not have been possible without the contributions of thousands of patients, whose participation in genetic research has enabled us to build a fundamentally new understanding of the cause of these diseases. With this financing we are positioned to rapidly advance our initial development candidates toward the clinic for patients.

The company will use the Series A funds to progress its first development candidates into IND-enabling studies, as well as to advance natural history studies to inform its clinical development plan and contribute to the scientific understanding of repeat expansion disorders.

More than 40 repeat expansion disorders have been identified, and most of these diseases are severe with limited to no treatment options, said Jean-Franois Formela, M.D., partner at Atlas Venture and Board Chair of Triplet. We have built Triplet to fundamentally transform what has been the treatment strategy for these diseases up to now.

The companys founding Board of Directors is comprised of:

Triplets launch today represents a turning point for the treatment of repeat expansion disorders. I look forward to working with this expert team to develop novel treatments for patients, said Shinichiro Fuse, Ph.D., partner at MPM Capital and member of Triplets Board of Directors.

This group of severe genetic disorders represents an area of high unmet medical need, and we look forward to working with Triplets leadership team as they reimagine the potential treatment paradigm for patients with rare diseases, said Laszlo Kiss, Ph.D., Pfizer Ventures principal and member of Triplets Board of Directors.

Triplet has also formed a Scientific Advisory Board comprised of leading investigators for repeat expansion disorders, including Sarah Tabrizi, Ph.D., professor of clinical neurology at University College London; Jim Gusella, Ph.D., Bullard Professor of Neurogenetics at Harvard Medical School; and Vanessa Wheeler, Ph.D., associate professor of neurology at Massachusetts General Hospital and Harvard Medical School.

About Triplet Therapeutics

Triplet Therapeutics is a biotechnology company developing transformational treatments for patients with unmet medical needs by leveraging insights of human genetics to target the underlying cause of repeat expansion disorders, a group of more than 40 known genetic diseases including Huntingtons disease, myotonic dystrophy and spinocerebellar ataxias. Triplet was founded by Nessan Bermingham, Ph.D., Atlas Venture and Andrew Fraley, Ph.D. Triplet has raised $59 million in funding to date, including its Series A funding in 2019 led by MPM Capital and Pfizer Ventures, with Atlas Venture, Invus, Partners Innovation Fund and Alexandria Venture Investments participating. Triplet is headquartered in Cambridge, Mass. For more information, please visit http://www.triplettx.com.

About Atlas Venture

Atlas Venture is a leading biotech venture capital firm. With the goal of doing well by doing good, we have been building breakthrough biotech startups for over 25 years. We work side by side with exceptional scientists and entrepreneurs to translate high impact science into medicines for patients. Our seed-led venture creation strategy rigorously selects and focuses investment on the most compelling opportunities to build scalable businesses and realize value. For more information, please visit http://www.atlasventure.com.

About MPM Capital

MPM Capital is a healthcare investment firm founding and investing in life sciences companies that seek to cure major diseases by translating scientific innovations into positive clinical outcomes. MPM invests in breakthrough therapeutics, with a focus on oncology. With its experienced and dedicated team of investment professionals, executive partners, entrepreneurs and scientific advisory board members, MPM is powering novel medical breakthroughs that transform patients lives. http://www.mpmcapital.com

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Triplet Therapeutics Launches with $59 Million in Financing to Further its Development of Transformative Treatments for Triplet Repeat Disorders -...

The first direct evidence of how bovine tuberculosis (TB) transmits infection between badgers and cattle has been revealed.

The research by scientists at UCD and the University of Edinburgh shows TB in cattle can be spread by badgers, but cow-to-cow transmission is much more significant than badger-to-cow.

TB in cattle and badgers passes between members of the same species at least twice as often than between cow and badger, the study finds.

Bovine TB is a chronic, highly infectious disease causing huge losses in affected farms in Ireland and the United Kingdom. The Irish control programme for bovine TB cost farmers, the exchequer and European Union 84 million in 2017.

The researchers examined genetic data from the bacteria that causes the disease also found cattle are approximately 10 times more likely to catch TB from badgers than badgers are to catch it from cattle.

The breakthrough should enable more focused management of badger populations, according to Dr Joseph Crispell of UCD School of Veterinary Medicine, a lead researcher in a study published on Tuesday in the journal eLife.

Culling of badgers to curb bovine TB is a contentious issue among veterinary and wildlife experts and animal welfare campaigners though the scientific and farming consensus is a wildlife reservoir of infected badgers sustains the disease, which originally began in cattle.

The research, which was conducted in Gloucestershire over a 15-year period, could improve control strategies, reduce disease transmission and cut associated costs, said Dr Crispell though further analysis needs to be conducted in different regions.

Their study was conducted in an area where there was known to be high badger populations while the same genetic and data collecting techniques were now being applied in Co Wicklow.

Bovine TB is an infectious respiratory disease of cattle mainly spread through inhaling infectious particles in the air. It is caused by the bacterium Mycobacterium bovis, which can also infect and cause disease in other mammals, including humans, deer, goats, pigs, cats and dogs.

Using data from an undisturbed population of badgers in Woodchester Park in Gloucestershire and nearby cattle farms, this study provides the first direct evidence of transmission between badgers and cattle. It is an area where tuberculosis is known to occur frequently in both cattle and badgers, he explained.

The researchers analysed the entire genetic make-up of the bacteria from 230 badgers and 189 cattle, a process known as whole genome sequencing. They combined this with detailed information on where the cattle and badgers lived, when they were infected, and whether they could have had contact with one another.

Scientists were then able to estimate how often the two species spread TB. They confirmed badgers play an important role in the maintenance of the disease in this area.

Prof Rowland Kao of the University of Edinburgh said the study provided not mere observation and inference but direct evidence that changes the nature of the game.

Current approaches to controlling bovine TB only discriminate at a very coarse, regional level between areas where badgers are more likely to be involved in infecting cattle from areas where they are not. This work identifies genetic signatures that could guide the interpretation of similar data if collected in other, less-intensively studied areas, he added.

This would allow for a more targeted control of tuberculosis in cattle and badgers, aiding efforts to control the disease and reduce the impact on the badger population Additional reporting Guardian

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Genetic clues of TB spread between cows and badgers revealed - Irish Times

When itwas unveiled in 2012, people had great hopes that the gene editor CRISPR/Cas9could treat or even cure hundreds to thousands of genetic diseases. This year,researchers in the United States began testing the gene editor in people, acrucial first step in determining whether the technology can fulfill itsmedical promise.

These first clinical trials are testing CRISPR/Cas9s safety and efficacy against cancer, blood disorders and one form of inherited blindness in people who already have the disease (SN: 8/31/19, p. 6). Many more such trials are expected to begin soon. Unlike the editing of human embryos that stirred up controversy in 2018 (SN: 12/22/18 & 1/5/19, p. 20), the genetic changes introduced in these trials would not be inherited by future generations.

CRISPRs rise as a potential medical tool happened inremarkably short time, says Janelle Waack, an intellectual property attorney atthe law firm Bass, Berry & Sims in Washington, D.C. She has been trackingthe dramatic growth of CRISPR patent filings, including for health care,medical research, agriculture and chemical processing. People are investing inthe technology and think it has great commercial value, she says.

These first tests in people are bellwethers of CRISPRsfuture, Waack says. Patients will benefit only if companies continue to investin the technology, and that investment may depend on whether these earlyclinical trials succeed.

CRISPR/Cas9 is a bacterial defense system against virusesthat scientists have repurposed to make precise changes to DNA in the cells ofhumans and other animals. A guide RNA tows the DNA-cutting enzyme Cas9 tospecific genes, where it slices through the DNA. In three clinical trials nowunder way in the United States, and one just completed, those cuts aredisabling genes or snipping out problem bits of DNA.

Results reported from the completed trial, led by researchers at the University of Pennsylvania, suggest that a CRISPR treatment designed to boost the cancer-fighting power of immune cells called T cells is safe. The results are from three patients two with multiple myeloma and one with sarcoma whose T cells were removed and edited in the lab. CRISPR disabled three genes in the T cells. Researchers then outfitted the cells with a warhead a gene that directs the cells to tumor cells that have a specific protein on their surfaces. While immune cells engineered to fight cancer, called CAR-Tcells, have been used in patients for years, souping up T cells with the help of CRISPR is a new innovation.

The findings, presented December 7 at the American Society of Hematology meeting in Orlando, Fla., showed that CRISPR-edited T cells took hold and reproduced in the cancer patients. None of the three people had any side effects associated with the cells. Thats good news since other revved-up T cells have caused high fevers, low blood pressure, seizures and other side effects (SN: 7/7/18, p. 22). However, the experimental treatment didnt slow the growth of the peoples cancers. Now that weve demonstrated safety and feasibility, well be much more focused on the effectiveness of the therapy, says Edward Stadtmauer, a hematologist and oncologist who led the trial.

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Similar tests of CRISPR-edited T cells are under way inChina. And CRISPR Therapeutics, a Cambridge, Mass.based company, expects tobegin three trials next year in which edited T cells target blood and kidneycancers, says Samarth Kulkarni, the companys chief executive officer.

CRISPR Therapeutics has already started trials with VertexPharmaceuticals, based in Boston and London, to remove and edit cells frompeople with the blood disorders sickle cell disease or beta-thalassemia. Theedits turn on production of fetal hemoglobin, usually made only until shortlyafter birth. Early results from one woman with beta-thalassemia and anotherwoman with sickle cell disease suggest that the edited cells are safe and makeenough fetal hemoglobin to relieve disease symptoms. While these data areearly, they show that this could be a onetime curative therapy for patients,Kulkarni said November 19 during a news briefing describing the results.

In another trial, researchers are snipping a small piece ofDNA out of cells in the eyes of people with an inherited form of blindnesscalled Leber congenital amaurosis 10. That DNA contains a mutation that causesthe blindness. The trial, conducted by Editas Medicine, also based inCambridge, Mass., and the global pharmaceutical company Allergan, is the first and for now, only trial using CRISPR to edit DNA directly in cells in thehuman body.

With direct editing, getting CRISPR to exactly the rightplace is the first challenge, Kulkarni says. From there, its impossible toknow whether the gene editor has made unwanted off-target edits as well.External editing allows researchers to check if the correct edits have beenmade, but the approach isnt feasible for many diseases.

Whether and how soon CRISPR becomes an accepted therapy, and how the U.S. government regulates the technology, may all depend in part on these initial trials. Everybody is paying careful attention, Waack says.

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The first U.S. trials in people put CRISPR to the test in 2019 - Science News

December 12, 2019 -Payers are using coordinated care and precision medicine to make diagnoses more quickly and ensure a strong treatment plan for severe and chronic disease management.

Early detection of chronic and severe diseases can mean the difference between life and death. It can also mean the difference between affordable therapies and crippling medical bills.

A March 2018 study found that early cancer diagnosis could result in significant cost savings nationally. Researchers looked at 17 types of cancer and estimated that early detection could save, conservatively, $26 billion nationally.

Recognizing what is at stake, payers take different approaches to catching severe or chronic illnesses in their formative stages.

Coordinated care is a simple, well-tested method for both chronic disease prevention and chronic disease management.

READ MORE: Chronic Disease Coordinated Care May Not Impact Pediatric Spending

Humana recently announced that it would pursue a traditional approach to ensure that patients in danger of chronic kidney and end of life renal disease find out early and get the support they need.

Humana will task skilled provider teams with catching these diseases earlier and implementing personalized treatments.

This coordinated care strategy builds a team of nephrologists, nurses, dietitians, and social workers from one of Humanas two partnerseither Monogram Health or Somatus, depending on geographic location.

The providers will work with the patients primary care physician to determine the best treatments and provide home healthcare options, patient education, and mental healthcare support through counseling.

This multidisciplinary approach will focus on detecting kidney disease earlier, slowing disease progression, and utilizing therapies that enable members to receive care in the convenience of their own home, said William Shrank, MD, MPHS, Humanas chief medical and corporate affairs officer.

READ MORE: Cigna and MSK Start Value-Based, Coordinated Cancer Care Program

Through this collaboration, we will strengthen care coordination for Humana members with kidney disease. Our partnerships will offer customized care options, and will empower patients with education and engagement tools to better manage their condition.

In February, Humana took a similar approach with its oncology program, enhancing its coordinated care strategy and using analytics to ensure quality care.

With new advancements every day in genetic therapies, precision medicine is another method payers use to ensure that patients receive a quick diagnosis and the best treatment plan.

CVS Health launched an oncology care program called Transform Oncology Care, which uses precision medicine to identify and treat cancer patients. The program is rolling out to Aetna members in 12 states but is also available for use by other payers.

Due to CVS Healths geographic and data footprint, it can assess the likelihood that a patient will get cancer. With that information, the patients provider can intervene early on to pursue preventive care, screenings, or therapies.

READ MORE: Precision Medicine Challenges Persist, Aetna Leads Response

When it comes to identifying the appropriate therapies, the program allows providers to use genetics to identify the best course of treatment for a patient recently diagnosed with cancer.

Timing in cancer care is everything and when a patient does not get started on the right treatment it can result in progression and higher costs, said Alan Lotvin, MD, executive vice president and chief transformation officer at CVS Health.

We are the first company working to make the latest in precision medicine accessible to more patients and further empower informed treatment decision-making based on a patient's genetic profile to give them the best chance for successful treatment and improved quality-of-life.

Working in coordination with its third-party vendor, Tempus, CVS Healths new program will enable patients to undergo a broad-panel gene sequencing test once diagnosed to determine the best treatment. This is ideal not only for patients in early stages of cancer, but especially for patients in more advanced stages who need to start treatment as soon as possible.

Because genomic sequencing has certain eligibility requirements, providers are not always aware that gene sequencing is an option open to their patient.

In order to ensure that oncologists prescribe gene sequencing to eligible patients, CVS Health introduced a web-based provider portal into its e-prescribing software which allows oncologists to see the patients eligibility for the broad-panel gene sequencing tests among other functions.

For those who qualify, the program identifies the best treatment options based on genetic makeup. It also alerts providers to potential clinical trials that patients can enroll in and makes the enrollment process easier and faster.

The program integrates National Comprehensive Cancer Network guidelines which are constantly updated for the most recent suggested prescribing and treatment options.

Critically, this service can be employed at the point of detection, so treatments can be identified immediately, and a therapeutic strategy quickly determined.

CVS Health combines this digital solution with a nurse-led coordinated care team to continue quality of care after the diagnosis.

This service is available for only fully insured commercial members.

Among its other chronic disease management developments, earlier this year, CVS Health used preventive care to improve diabetes treatment.

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Care Coordination and Precision Medicine Improve Early Diagnoses - HealthPayerIntelligence.com

A genetic variant found in about 3% of people of African ancestry is a more significant cause of heart failure than previously believed, according to a multi-institution study led by researchers at Penn Medicine. The researchers also found that this type of heart failure is underdiagnosed. According to their study, 44% of TTR V122Ivariant carriers older than age 50 had heart failure, but only 11% of these individuals had been diagnosed with hATTR-CM. The average time to diagnosis was three years, indicating both high rates of underdiagnoses and prolonged time to appropriate diagnosis

This study suggests that workup for amyloid cardiomyopathy and genetic testing of TTR should be considered, when appropriate, to identify patients at risk for the disease and intervene before they develop more severe symptoms or heart failure, said the studys lead author Scott Damrauer, M.D., an assistant professor of Surgery at Penn Medicine and a vascular surgeon at the Corporal Michael J. Crescenz VA Medical Center. (Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania and the University of Pennsylvania Health System.)

In this study, researchers from Penn Medicine and the Icahn School of Medicine at Mount Sinai used a genome-first approach, performing DNA sequencing of 9,694 individuals of African and Latino ancestry enrolled in either the Penn Medicine BioBank (PMBB) or the Icahn School of Medicine at Mount Sinai BioMe biobank (BioMe). Researchers identified TTR V122I carriers and then examined longitudinal electronic health record-linked genetic data to determine which of the carriers had evidence of heart failure.

The findings, which were published today in JAMA, are particularly important given the US Food and Drug Administrations (FDA) approval of the first therapy (tafamidis) for ATTR-CM in May 2019. Prior to tafamidiss approval, treatment was largely limited to supportive care for heart failure symptoms and, in rare cases, heart transplant.

Our findings suggest that hATTR-CM is a more common cause of heart failure than its perceived to be, and that physicians are not sufficiently considering the diagnosis in certain patients who present with heart failure, said the studys corresponding author Daniel J. Rader, M.D., chair of the Department of Genetics at Penn Medicine. With the recent advances in treatment, its critical to identify patients at risk for the disease and, when appropriate, perform the necessary testing to produce an earlier diagnosis and make the effective therapy available.

hATTR-CM, also known as cardiac amyloidosis, typically manifests in older patients and is caused by the buildup of abnormal deposits of a specific transthyretin protein known as amyloid in the walls of the heart. The heart walls become stiff, resulting in the inability of the left ventricle to properly relax and adequately pump blood out of the heart. However, this type of heart failurewhich presents similar to hypertensive heart disease is common, and the diagnosis of hATTR-CM is often not considered.

Tafamidis meglumine is a non-NSAID benzoxazole derivative that binds to TTR with high affinity and selectivity. TTR acts by transporting the retinol-binding protein-vitamin A complex. It is also a minor transporter of thyroxine in blood. Its tetrameric structure can become amyloidogenic by undergoing rate-limiting dissociation and monomer misfolding.

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Penn Team Finds Genetic Variant Largely Found in Patients of African Descent that Increases Heart Failure Risk - Clinical OMICs News

ByGreg Rienzi

STOCKHOLMA small group of men clutching notebooks and folders gathered Thursday afternoon outside Stockholm's Grand Hotel, a 145-year-old luxe waterfront accommodation in the historic city's Old Town. They were autograph hunters, and many had been there for hours in the December cold waiting for the signatures of the hotel's guests of honor. Since 1901, the Grand Hotel has hosted Nobel laureates and their families, and Thursday was arrival day in Sweden's capital for most of this year's 14 award winners.

As the skies darkened and the biting Baltic Sea winds whipped across the Vartan Strait, the crowd of autograph hounds only grew. One such gentleman, a 70-year-old freelance photographer named Hans, has stood outside the hotel on arrival day every year since 1976, when he collected the signature of Saul Bellow, that year's winner of the Nobel Prize for literature. In a well-worn red notebook, he held signatures of dozensperhaps hundredsof laureates including author Alice Munro and British biochemist Gregory Winter. The next one he sought would go on a photo he kept in a folder. "I hope he will sign," Hans said, pointing to the name he'd written in black marker, Gregg L. Semenza.

Minutes later, the Johns Hopkins School of Medicine professor and winner of the 2019 Nobel Prize for physiology or medicine gladly obliged, signing a dozen autographs or more just moments after he was whisked out of a Volvo XC40 SUV, the official car of Nobel Week, and onto the red carpet accompanied by his wife, Laura Margaret Kasch-Semenza. Other bystanders whipped out their phones and cameras to capture the moment. Semenza had been in Stockholm less than an hour, and he was already getting the rock star treatment.

Video credit: Len Turner and Dave Schmelick

In this city, the home and birthplace of the Nobel Prize, laureates are treated as celebrities, and the associated ceremonies are as much a part of popular culture in Sweden as the Academy Awards are in the U.S. After laureates arrive in Stockholm, they face a gauntlet of a schedule that includes press conferences, champagne receptions, lectures, a concert, school visits, and a trip to the Swedish Riksdag (parliament), all leading up to the grand white-tie affair award ceremony held on Dec. 10 at the Stockholm Concert Hall. Laureates will also participate in Nobel Minds, a roundtable TV discussion that is celebrating its 60th anniversary this year.

Annika Pontikis, director of communications for the Nobel Foundation, said the week is a whirlwind for each award recipient, most of whom are certainly not used to this level of attention and pageantry.

"There is a lot of expectation in the air when they arrive in Stockholm," Pontikis said. "We do our best to prepare them before and after they arrive for what is about to happen. The people of Sweden have been looking forward to this."

Image credit: Will Kirk / Johns Hopkins University

To keep them on schedule and handle all the small details, each laureate is assigned a personal attach, a young diplomat from the Swedish foreign ministry who meets them the moment they step off the plane and stays with them for the entirety of their stay.

So began the Nobel Week journey for Semenza, 63, who earned the prize for the groundbreaking discovery of the gene that controls how cells respond to low oxygen levels. Semenza shares the award, and the $913,000 cash prize, with William G. Kaelin Jr. and Sir Peter J. Ratcliffe.

Considered among the most prestigious awards in the world, Nobel Prizes have been awarded for achievements in physics, chemistry, physiology or medicine, literature, and peace since 1901 by the Nobel Foundation in Stockholm. A total of 916 individuals and 24 organizations have received the prize named in memory of Sweden's own Alfred Nobel, a businessman, chemist, engineer, and inventor known for the discovery of dynamite.

The week officially kicked off Thursday with a morning press event held at the Nobel Prize Museum in the Old Town. On hand were representatives of the Nobel Foundation and some of the week's key participants, including Sebastian Gibrand, chef for the Nobel Banquet who won the silver medal earlier this year at the Bocuse d'Or, the world's most prestigious international culinary competition. For this year's banquet menu, Gibrand and a team of 40 chefs will focus on locally sourced ingredients from Swedish producers to feed the 1,300-plus guests, including the Swedish Royal Family.

"We will use everything from root to top, and nose to tail, to make sure we use all of the product and nothing goes to waste," said Gibrand, adding what a great honor it was to be hosting the prestigious dinner he views as a symbol of peace.

On Friday morning, the Nobel laureates visited the Nobel Prize Museum, where they each autographed a chair in the museum's restaurant and donated a specially selected artifact to the museum's collection. Semenza donated a 27-year-old autoradiogram, an image on an X-ray film produced by the pattern of decay emissions from a distribution of radioactive phosphorus. This particular image, he said, was a critical step in the discovery of hypoxia-inducible factor 1, or HIF-1, which has far-reaching implications in understanding the impact of decreased oxygen levels in blood disorders, cancer, diabetes, coronary artery disease, and other conditions.

Complete coverage

As Johns Hopkins physician-scientist Gregg Semenza travels to Stockholm to accept his Nobel Prize, the Hub takes readers along for the journey, from his arrival in Sweden to his Nobel lecture to the grand Nobel Award ceremony and banquet

Erika Lanner, CEO and director of the Nobel Prize Museum, said the artifacts give the museum's visitors an opportunity to learn more about the discoveries and works that the laureates are rewarded for.

"We are mainly a museum of stories and ideas," Lanner said. "These objects that we humbly ask the Nobel laureates to donate to us bring life, meaning, and body to these stories, which we hope will serve as inspiration for a young audience. They also help us understand and get closer to the person, which is important in itself."

The Nobel Prize is so unique and special, Lanner said, because it underscores the impact one individual can have.

"The Nobel Prize is about the possibilities for ideas to change the world," she said.

Image caption: A crowd gathers outside the Nobel Museum to catch a glimpse of the laureates as they attend a private welcoming ceremony Friday

Image credit: Will Kirk / Johns Hopkins University

Weeks before he left for Stockholm, Semenza said that he was looking forward to the gamut of events leading up to the award celebration. In many ways, life had already changed for the modest researcher, who has gotten used to posing for pictures and selfies everywhere he goes.

"In a way, it will be more hectic than it's already been for me, but I feel we've had so much preparation for that week and a half. It will be good just to be on autopilot and have an attach to tell me what to do every step of the way. And I'm very good at taking orders," Semenza said with a laugh.

He said he was most excited about taking in the once-in-a-lifetime experience with family, friends, and mentors who helped make his discovery possible, and who he hoped would enjoy the memorable experience as much as he would. Johns Hopkins will be well represented among Semenza's guests in Stockholm, who include JHU President Ronald J. Daniels; Paul B. Rothman, dean of the medical faculty and CEO of Johns Hopkins Medicine; Charles Wiener, professor of medicine and president of Johns Hopkins Medicine International; Haig Kazazian, professor of genetic medicine; Landon King, professor of medicine and executive vice dean for the School of Medicine; Ted Dawson, professor of neurology and director of the Institute for Cell Engineering; and David Valle, professor of genetic medicine and director of the Institute of Genetic Medicine.

Image caption: The Nobel Prize award ceremony is a highly formal affair. Semenza is fitted for a white tie tuxedo with tails.

Image credit: Will Kirk / Johns Hopkins University

Shortly after his Thursday arrival, Semenza was driven to Hans Allde tailor shop in the city's business district to be fitted for the tuxedo that he will wear on the day of the award ceremony and banquet. He was fitted personally by owner Lars Allde, the son of the store's founder, who has worked with the majority of Nobel laureates since 1982.

Semenza looked relaxed and beaming as he entered the store, greeted as a VIP and introduced to the official photographer of 2019 Nobel Prize winners, who told him: "Get used to me. I will be with you every step of the way."

The visit was a brief onehis only big decision was what type of bow tie he would wear. Semenza left the store eager to return to his hotel, get some sleep, and prepare for what lies ahead.

"Tomorrow we get going for sure," he said. "I'm really looking forward to it."

Continued here:

For Nobel laureates, a whirlwind welcome - The Hub at Johns Hopkins

ByGreg Rienzi

STOCKHOLMDuring his distinguished career, Gregg Semenza has given hundreds of lectures. In fact, for general scientific audiences, the Johns Hopkins University School of Medicine professor often gives a longer version of the very talk he presented on Sundaydetailing his discovery of the HIF-1 protein's role in human cell oxygen level regulationduring his Nobel Prize lecture at the Karolinska Institutet's Aula Medica auditorium.

But he's never presented to such a large crowd, let alone for such a crowning career achievement.

At the end of his Nobel Prize lecture, where in 30 minutes he effortlessly synthesized three decades of research on how the human body adapts to changes in oxygen availability, Semenza took ample time to thank the many people responsible for bringing him to this moment.

He dedicated his lecture to his high school biology teacher, Rose Nelson, pictured prominently in a slide of the many scientists whom he learned from.

Video credit: Len Turner and Dave Schmelick

"Dr. Nelson was my inspiration in science. I'm here because of her," Semenza told the crowd. He also thanked his early mentors at Johns Hopkins, chiefly professors of genetic medicine Haig Kazazian and Stylianos Antonarakis, both in the audience, and the late Victor McKusick, hailed as the "father of medical genetics." Indeed, the list of acknowledgments was long and detailed, naming nearly 150 faculty colleagues as well as students and postdocs who have collaborated with him over the years.

But before he was done, Semenza flashed a slide of his familyof him with his wife and three childrentaken on the beach during a vacation to Maine this past summer. "And last but not least, I'd like to thank " he began before pausing, tears welling in his eyes, voice cracking. He bowed his head briefly. In an instant, the emotion of the moment overtook him. Sensing the heartfelt struggle, the packed house of more than 800 attendees came to his aid with a roar of applause.

"Thank you," Semenza said, before pausing to take in a deep breath. "OK. I've got it together. I'd like to thank my wife, Laura; my sons, Evan and Gabe; my daughter, Allie, for always being there for me. Giving me unconditional love and support."

The moment was out of character for the usually reserved physician-scientist, but it gave a hint of the many emotions bubbling just beneath the surface during perhaps the most momentous week of his life.

"At that moment, I was feeling the power of my feelings for those people, particularly for my family, and it just became really kind of overwhelming," Semenza said the next morning. "That's never happened to me before. ... It caught me by surprise."

Video credit: Nobel Prize

On many occasions, Semenza has said sharing this Nobel Prize experience with family and friends is the pinnacle of the trip. A group of 30 family members and close friends have traveled to Stockholm to celebrate the week with him, including his four siblings, his mother, and her twin sister.

Beth Murphy, Semenza's sister, said it was both touching and surprising to see her older brother break down on stage, if only for a moment.

"It's not like him, for him to tear up like that," she said. "But obviously he went someplace deep inside of him."

She added that it's already been an emotional few days for their family as they share this unique experience with him, touring Stockholm and taking part in Nobel Week activities.

"I really, really love seeing how happy Gregg is," she said. "This is his life's work. To see him smiling from ear to ear the whole time is just fabulous."

Image credit: Will Kirk / Johns Hopkins University

Semenza's siblings have said the fame and attention of receiving science's highest honor have certainly not gotten to their brother, who has been celebrated at nearly every turn since he received news of the award in early October.

"He's the same humble, hardworking, and quiet guy he's always been," said brother Matt Semenza. "For us, it's been very exciting. I got to see him win the Gairdner Award [for Biomedical Research] in Toronto and the 2016 Albert Lasker Basic Medical Research Award in New York. So this is like the apogee of the award road trip we've been on with him."

Laurene Graig, Semenza's sister, added that while the emotional moment on stage might have been out of character, her brother's unselfishness and humility are not.

"I really appreciate that [Gregg] has recognized all the people who have helped and supported him along the way," she said. "I think it takes a certain amount of grace to do that. I'm very proud of him. We all are. There's been a lot of 'we' when he talks, not 'I' or "my.'"

Image caption: Semenza (center) with his family

Image credit: Will Kirk / Johns Hopkins University

When asked about his accomplishments and research, Semenza frequently credits others, and considers himself fortunate to happen upon the discoveries that brought him to this point. He traces it all back to his days growing up in New York.

Born in New York City in 1956, Semenza spent his formative years in Tarrytown, New York, a village located in Westchester County along the Hudson River. Semenza called it a "great place to grow up," a small-town atmosphere only a few train stops away from New York City where he would often go on the weekends to tour museums. His mother, Kathryn, taught at an elementary school, so learning and education were always priorities for the young Semenza.

At Sleepy Hollow High School, he learned to love science from Nelson, who during his junior year alerted him to an opportunity to take part in a National Science Foundation summer program at the Boyce Thompson Institute for Plant Research, an independent research institute then located in Yonkers, New York, and now located on the campus of Cornell University in Ithaca.

There he would do simple experiments like exposing plants to viruses and detailing the signs of infection.

"I was all thumbs back then because this was the first time I'd done it," Semenza said. "But I still enjoyed it. And this experience was really important for me because it showed me this was something I'd like to do for a career. It was just one more link in the chain of events that led me on the path that ended up here."

This exposure to science at such a young age, and the mentoring he received from Nelson, is largely why Semenza now champions STEM education and the teaching profession. That was what compelled him to not only dedicate his Nobel Prize lecture to Nelson, he said, but also to share the long list of undergraduate students, graduate students, and postdocs who have worked with him over the past three decades at Johns Hopkins.

"I stopped doing experiments in my lab back in 1996," he said. "Since then, all the data has been generated by students and trainees. I can have all the greatest ideas in the world, but science is about generating data. If I didn't have all these people doing that, all these ideas wouldn't matter. We're not philosophers. We're scientists. If we have an idea, if we have a hypothesis, we have to prove it."

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As Johns Hopkins physician-scientist Gregg Semenza travels to Stockholm to accept his Nobel Prize, the Hub takes readers along for the journey, from his arrival in Sweden to his Nobel lecture to the grand Nobel Award ceremony and banquet

Mentoring students, he says, has been vitally important to him, as he feels the need to repay the debt of what his mentors did for him and pay it forward to the next generation.

That next generation was notably present at his Nobel Prize lecture, a celebration of science that many consider the most exciting part of the week as people get to hear directly from the Nobel laureates about their significant contributions to their fields. A long line of mostly students and young researchers snaked around the Aula Medica building that day, down steps and around the block, students such as Stephanie Chanda, a first-year biomedicine master's student at the Karolinska Institutet who had been in line with friends for hours to ensure she got in and got a good seat. "Of course, we are very interested in the Nobel lecture because we want to be researchers ourselves one day," Chanda said.

Also in the crowd were Semenza's family and friends and colleagues, including several of those he thanked in his talk.

"Having family and friends here is really the most important part of this experience, sharing this with them," Semenza said. "It's been great to have [my mom] here. Nobody has been more excited than she has. She's become something of a local celebrity back in Tarrytown, appearing in all the media, newspaper and television. ... She's very into it. And she deserves the attention.

"It's been an exciting week," he added, "from the time we stepped out of the car at the Grand Hotel to the throng of autograph seekers standing out in the cold waiting for us to come, to the thrill of giving the Nobel lecture yesterday. And having so many friends and family here to enjoy it with. That's really what has made it most special for me."

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A Nobel journey a lifetime in the making - The Hub at Johns Hopkins