StemCell Therapy

P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center, works in his lab. Credit: Dan Addison | UVA

Scientists at the University of Virginia School of Medicine have discovered a strange new organelle inside our cells that helps to prevent cancer by ensuring that genetic material is sorted correctly as cells divide.

The researchers have connected problems with the organelle to a subset of breast cancer tumors that make lots of mistakes when segregating chromosomes. Excitingly, they found their analysis offered a new way for doctors to sort patient tumors as they choose therapies. They hope these insights will allow doctors to better personalize treatments to best benefit patients sparing up to 40 percent of patients with breast cancer, for example, a taxing treatment that wont be effective.

Some percentage of women get chemotherapy drugs for breast cancer that are not very effective. They are poisoned, in pain and their hair falls out, so if it isnt curing their disease, then thats tragic, said researcher P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center. One of our goals is to develop new tests to determine whether a patient will respond to a chemotherapeutic treatment, so they can find an effective treatment right away.

The organelle Stukenberg and his team have discovered is essential but ephemeral. It forms only when needed to ensure chromosomes are sorted correctly and disappears when its work is done. Thats one reason scientists havent discovered it before now. Another reason is its mind-bending nature: Stukenberg likens it to a droplet of liquid that condenses within other liquid. That was the big wow moment, when I saw that on the microscope, he said.

These droplets act as mixing bowls, concentrating certain cellular ingredients to allow biochemical reactions to occur in a specific location. Whats exciting is that cells have this new organelle and certain things will be recruited into it and other things will be excluded, Stukenberg said. The cells enrich things inside the droplet and, all of a sudden, new biochemical reactions appear only in that location. Its amazing.

P. Todd Stukenberg, PhD, of UVAs Department of Biochemistry and Molecular Genetics and the UVA Cancer Center, discovered an unknown organelle in our cells that helps ensure genetic material is sorted correctly when cells divide. Credit: Dan Addison | UVA

Its tempting to think of the droplet like oil in water, but its really the opposite of that. Oil is hydrophobic it repels water. This new organelle, however, is more sophisticated. Its more of a gel, where cellular components can still go in and out but it contains binding sites that concentrate a small set of the cells contents, Stukenberg explained. Our data suggests this concentration of proteins is really important. I can get complex biochemical reactions to occur inside a droplet that Ive been failing to reconstitute in a test tube for years. This is the secret sauce Ive been missing.

While its been known for about eight years that cells make such droplets for other processes, but it was unknown that they make them on chromosomes during cell division. Stukenberg believes these droplets are very common and more important than previously realized. I think this is a general paradigm, he said. Cells are using these non-membranous organelles to regulate much of their work.

In addition to helping us understand mitosis how cells divide Stukenbergs new discovery also sheds light on cancer and how it occurs. The organelles main function is to fix mistakes in tiny microtubules that pull apart chromosomes when cells are dividing. That ensures each cell winds up with the correct genetic material. In cancer, though, this repair process is defective, which can drive cancer cells to get more aggressive.

He has also developed tests to measure the amount of chromosome mis-segregation in tumors, and he hopes that this might allow doctors to pick the proper treatment to give cancer patients. We have a way to identify the tumors where the cells are mis-segregating chromosomes at a higher rate, he said. My hope is to identify the patients where treatments such as paclitaxel are going to the most effective.

Having looked at breast cancer already, he next plans to examine the strange organelles role in colorectal cancer.

###

Stukenberg and his colleagues have described their discovery in the scientific journal Nature Cell Biology. The research team consisted of Prasad Trivedi, Francesco Palomba, Ewa Niedzialkowska, Michelle A. Digman, Enrico Gratton and Stukenberg.

Reference: The inner centromere is a biomolecular condensate scaffolded by the chromosomal passenger complex by Prasad Trivedi, Francesco Palomba, Ewa Niedzialkowska, Michelle A. Digman, Enrico Gratton and P. Todd Stukenberg, 3 September 2019, Nature Cell Biology.DOI: 10.1038/s41556-019-0376-4

The research was supported by the National Institutes of Health, grants R01GM124042, R24OD023697 and P41-GM103540; and the National Science Foundation, grant MCB-1615701.

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Strange New Organelle That Helps Prevent Cancer Discovered in Our Cells - SciTechDaily

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

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

Image source: Getty Images.

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

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

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

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

Clinical Consideration

CRISPR-CasX Gene Editing

CRISPR Base Editing

Does it cut DNA?

Yes, enzymatically cuts both strands of DNA

No

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

Yes

No, but it can enzymatically change an existing DNA sequence

Does it trigger DNA repair mechanisms?

Yes

No

Source: Beam Therapeutics, author.

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

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

Image source: Getty Images.

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

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

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

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

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

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

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

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

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

Dr. Lu Qi is director of the Tulane University Obesity Research Center at Tulane School of Public Health and Tropical Medicine.

Getting a good nights sleep could be beneficial for long-term health. A pioneering new study led by Dr. Lu Qi, director of the Tulane University Obesity Research Center, found that even if people had a high genetic risk of heart disease or stroke, healthy sleep patterns could help offset that risk. The study is published in the European Heart Journal.

The researchers looked at genetic variations known as SNPs (single nucleotide polymorphisms) that were already known to be linked to the development of heart disease and stroke. They analysed the SNPs from blood samples taken from more than 385,000 healthy participants in the UK Biobank project and used them to create a genetic risk score to determine whether the participants were at high, intermediate or low risk of cardiovascular problems.

The researchers followed the participants for an average of 8.5 years, during which time there were 7,280 cases of heart disease or stroke.

We found that compared to those with an unhealthy sleep pattern, participants with good sleeping habits had a 35% reduced risk of cardiovascular disease and a 34% reduced risk of both heart disease and stroke, Qi says. Researchers say those with the healthiest sleep patterns slept 7 to 8 hours a night, without insomnia, snoring or daytime drowsiness.

When the researchers looked at the combined effect of sleep habits and genetic susceptibility on cardiovascular disease, they found that participants with both a high genetic risk and a poor sleep pattern had a more than 2.5-fold greater risk of heart disease and a 1.5-fold greater risk of stroke compared to those with a low genetic risk and a healthy sleep pattern. This meant that there were 11 more cases of heart disease and five more cases of stroke per 1,000 people a year among poor sleepers with a high genetic risk compared to good sleepers with a low genetic risk. However, a healthy sleep pattern compensated slightly for a high genetic risk, with just over a two-fold increased risk for these people.

A person with a high genetic risk but a healthy sleep pattern had a 2.1-fold greater risk of heart disease and a 1.3-fold greater risk of stroke compared to someone with a low genetic risk and a good sleep pattern. While someone with a low genetic risk, but an unhealthy sleep pattern had 1.7-fold greater risk of heart disease and a 1.6-fold greater risk of stroke.

As with other findings from observational studies, our results indicate an association, not a causal relation, Qi says. However, these findings may motivate other investigations and, at least, suggest that it is essential to consider overall sleep behaviors when considering a persons risk of heart disease or stroke.

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Can good sleep patterns offset genetic susceptibility to heart disease and stroke? - News from Tulane

In the world of rare diseases, patient testimonies about the extreme difficulties of receiving an accurate diagnosis for an illness are numerous. For instance, one woman, sick for most of her young life, was not properly diagnosed with idiopathic gastroparesis an ultra-rare disease that affects stomach motility and digestion until late in college after seeing numerous different specialists in multiple fields and undergoing a battery of testing.1 Another patient, now active in the rare disease advocacy community, went undiagnosed with familial partial lipodystrophy a disease that, among other things, causes selective fatty tissue loss for 37 years.2

Unfortunately, these stories are not unique. One survey indicated that it took on average 7.6 years to properly diagnose a rare disease patient in the United States.3 Another study indicated that a rare disease patient on average consulted eight different physicians before landing on an accurate diagnosis, with only 12.9 percent of respondents indicating that they had seen only one physician prior to diagnosis (23.5 percent of respondents had seen between six and 10 physicians).4 Frequently, rare disease patients exhibit similar symptoms as other, more common diseases, making diagnosis complicated and leaving patients confused and frustrated about a path forward. Further complicating the situation is that traditional treatments for more common illnesses that mimic rare disease symptoms, such as irritable bowel syndrome in the case of the aforementioned gastroparesis patient, may actually worsen a patient's condition.

As such, the misdiagnosis of rare diseases, in addition to being traumatic for patients and their families, can be extremely expensive. One study indicated that over a 10-year period, an undiagnosed rare disease patient cost over 100 percent more than the average patient. This was due in part to a significant increase in outpatient visits compared with the average patient. (The cost differential was heightened in pediatric patients.)5 Such data indicates that shortening the path to diagnosis for rare disease patients may lead not only to increase patient health but also to a significant reduction in overall long-term healthcare costs.

According to the National Institutes of Health (NIH), there may be upward of 7,000 rare diseases in the United States affecting as many as 30 million people, or nearly one-tenth of the U.S. population.6 Alarmingly, only 5 percent of identified rare diseases have an approved treatment. Despite this daunting figure, approximately 80 percent of rare diseases have genetic origins, a common factor that points to genetic (the testing of individual variants or individual/multiple genes and their effects on an individual) and genomic (the study through various methods of an individual's entire genome and its interaction with the environment) testing as logical tools for identifying and ultimately combating these illnesses.

Genetic Testing Becoming More Common

From concept to execution, the Human Genome Project at the NIH took approximately 15 years and involved the creation of the National Center for Human Genome Research (now the National Human Genome Research Institute, an official Institute at NIH), the collaboration of hundreds of national and international scientists, and an approximate, inflation-adjusted total investment of $5 billion.7,8Since that time, the cost of performing genetic and genomic testing has declined significantly, with a per-genome cost of slightly less than $1,000 in 2019 compared with per-genome costs of approximately $95 million and $30,000 in 2001 and 2010, respectively.9 This significant cost reduction, which has been associated with the development of next-generation sequencing platforms and leaps in computer hardware development, among other things, has opened the door for patients to more readily access these important resources.

Most tests fall into overall categories of DNA diagnostic testing that include single-gene tests, which can detect an abnormality in a gene associated with a particular genetic illness; whole exome sequencing, which sequences the protein-encoding regions of genes; or whole genome sequencing, which is the most rigorous in that it involves sequencing the individual's entire genome. Given the sheer number of rare diseases and the size of the human genome, it is not surprising that there are numerous genetic tests on the market today. One study indicated that there are approximately 75,000 genetic tests on the market, or 10 issued every day.10

However, insurance coverage for these technologies is minimal and inconsistent despite recent positive reception for the increased use of enhanced technologies for patient treatment through the Precision Medicine Initiative, the NIH's Cancer Moonshot and similar programs. One study indicated that coverage for multigene testing varied drastically by disease type and that tests for broad indications or a large range of genes (i.e., those tests that may be helpful in narrowing down disease possibilities in a diagnostic profile) are frequently not covered by insurers.11 It should be noted that some progress has been made on national coverage determinations for some more widely recognized testing technologies. For instance, next-generation sequencing, a revolutionary sequencing technology that sequences genetic material multiple times simultaneously against a reference genome, received a reissued national coverage determination under the Medicare program from the Centers for Medicare & Medicaid Services (CMS) in October 2019.12 However, while this decision was significant as a model for future coverage for genetic testing services, it was only a minor first step in that it was limited only to previously untested patients with ovarian or breast cancer who are Medicare eligible.13

The large and complicated landscape of genetic testing is partially responsible for the lack of insurance coverage for these technologies. For instance, there are only about 200 standardized Current Procedural Terminology (CPT) codes to identify various types of genetic tests to insurers, other physicians, hospitals and health systems, limiting the ability for payers to systematically cover these technologies. This is especially true when applying "medical necessity criteria," which requires a provider to submit accurate information showing that a treatment or test is medically necessary to treat or diagnose a specific illness in order for it to be reimbursed by a payer. Data have shown that a majority of spending in the past several years on genetic tests has gone to noninvasive prenatal tests, cancer screening tests and multiple-gene analyses.14 This is unsurprising given that some of these technologies target pre-identified, validated markers and that newer screening methods present fewer risks for patients than other, more traditional or invasive testing methods.15 For many conditions, however, showing the medical necessity of genetic testing is still a complicated and unpredictable process when a patient is in the middle or beginning of his or her diagnostic odyssey.

Thus, coverage of new genetic testing technologies continues to remain a major challenge for the medical community and a mystery for the tens of millions of U.S. patients with rare diseases. Although small-scale studies and other evidence show that the use of genetic testing as a means to more quickly and accurately diagnose patients can reduce overall health expenditures, policymakers still lack systematic data showing the effectiveness of genetic testing as a means of cutting overall health spending at a macro level.

Help on the Horizon?

Bills have been introduced as recently as the 116th Congress that would create demonstration projects to test coverage of genetic testing technologies for certain patients to help inform future expansions of genetic testing coverage. In addition, Reps. Diana DeGette (D-Colo.) and Fred Upton (R-Mich.), the original champions of the 21st Century Cures Act,16 recently issued a request for information to help inform a follow-on version of the landmark legislation dubbed "Cures 2.0."17 One of the main focuses of their inquiry is into "how Medicare coding, coverage, and payment could better support patients' access to innovative therapies." Expanded coverage to increase access to genetic testing technologies could certainly fit within this scope and would help supplement expanded access and coverage of other new and innovative healthcare technologies for rare disease patients.

Stakeholders across the rare disease landscape have also shared consistent concerns with the length of time between when a new or breakthrough medical technology is approved and when it receives coverage by insurers. Underutilized programs may help speed new technologies to the patients that need them by shortening the gap between approval and coverage. One such example is the U.S. Food and Drug Administration (FDA)-CMS parallel review program for medical devices, which was recently touted by U.S. Department of Health and Human Services (HHS) Deputy Secretary Eric Hargan at the recent FDA/CMS Summit18 and through which a next-generation sequencing test received a parallel approval and coverage determination in 2017.19 These efforts may help the scientific community and others assemble data about how greater access to these technologies positively affect patient care, provide information necessary for lawmakers to empower CMS, the FDA and others to work together on increasing coverage and access, as well as to create mechanisms to speed new technologies to patients in need.

In addition to testing expansion of coverage and access for genetic and genomic testing, further investments should be made into public-private partnerships and other information gathering networks that may centralize information from a diverse group of medical professionals to provide patients additional resources for rare disease diagnosis. For instance, the Undiagnosed Diseases Network, housed at the NIH, utilizes a dozen sites nationwide where teams of physicians assess rare disease patients and share data, including genetic testing data through a "sequencing core," to maximize the amount of national expertise available to pin down rare disease diagnoses that would be extremely difficult and expensive to receive if patients sought expertise individually.20 In addition to further investment in these resources, continued policy development and investment in the development of artificial intelligence technologies and diagnostic support software tools, which have shown promise in assisting physicians in the early detection of rare disease through symptom analysis,21 will provide additional means for patients to receive care more quickly through largely noninvasive means.

Finally, payers both public and private may lack expertise in understanding and evaluating genetic tests, especially for rare diseases. Insurers should prioritize hiring individuals to supplement their teams who have some form of advanced knowledge not only of rare diseases but also the nature of genetic testing technologies and how they are used to expedite disease diagnoses. This is especially true given the rapid development of new testing systems and the growing use of other diagnostic technologies promoted in part by provisions in the 21st Century Cures Act and other legislation.

While it typically refers to something that is uncommon, the term "rare" can also imply heightened value. Greater investment in improving the diagnostic odyssey for rare disease patients, including through greater coverage of new technologies, can only enhance the value and efficiency of the U.S. healthcare system for all patients not just the few.

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Sequence of Events: Genetic Testing Offers Significant Promise, But Coverage and Access Limited - Lexology

By Michael Erman

NEW YORK (Reuters) Novartis is in discussion with patient groups over its lottery-style free drug program for its multi-million-dollar gene therapy for spinal muscular atrophy (SMA) after criticism that the process could be unfair to some babies with the deadly disease.

The company said on Friday that it will be open to refining the process in the future, but it is not making any changes at this time. The program is for patients in countries where the medicine, called Zolgensma, is not yet approved for the rare genetic disorder, which can lead to death and profound physical disabilities.

At $2.1 million per patient, Zolgensma is the worlds costliest single-dose treatment.

Novartis said the program will open for submission on Jan. 2 and the first allocation of drugs would begin in February. Novartiss AveXis unit, which developed the drug, will give out 50 doses of the treatment through June for babies under 2 years old, it said on Thursday, with up to 100 total doses to be distributed through 2020.

Patient advocacy group SMA Europe had a conference call with the company on Friday, according to Kacper Rucinski, a board member of the patient and research group who was on the call.

There are a lot of ethical questions, a lot of design questions that need to be addresses. We will be trying to address them in January, Rucinski said. He said the program has no method of prioritizing who needs the treatment most, calling it a Russian roulette.

The company said it developed the plan with the help of bioethicists with an eye toward fairness.

This may feel like youre blindly passing it out, but it may be the best we can do, said Alan Regenberg, who is on the faculty at Johns Hopkins Berman Institute of Bioethics and was not among the bioethicists Novartis consulted with on the decision. It may be impossible to separate people on the basis of prognosis out of the pool of kids under 2, he said.

According to Rucinski, the parties will continue their discussion in January to see what can be improved in the design of the program.

Novartis said on Thursday that because of manufacturing constraints it is focused on providing treatment to countries where the medicine is approved or pending approval. It has one licensed U.S. facility, with two plants due to come on line in 2020.

Zolgensma, hit by turmoil including data manipulation allegations and suspension of a trial over safety concerns, is the second SMA treatment, after Biogens Spinraza.

Not all of the SMA community are opposed to Novartis program.

Rajdeep Patgiri moved from the United Kingdom to the United States in April so his daughter could receive Zolgensma. She has responded well to the treatment, and Patgiri worries that negative attention to the program could keep patients from receiving the drug.

The best outcome for all patients would be if everybody could get the treatment. Given all the constraints, a lottery is probably the fairest way to determine who receives the treatment, he said.

(Reporting by Michael Erman; Additional reporting by John Miller in Zurich; Editing by Leslie Adler)

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Novartis in talks with patients upset about lottery-like gene therapy giveaway - Physician's Weekly

This years Clinical Trials on Alzheimers Disease meeting began in mid-December with a bang and ended a few days later with hallway conversations laced with worry. The topic, in both cases, was aducanumab, an experimental drug for treating people with Alzheimers disease.

The meeting got off to celebratory start as a top Biogen scientist presented results showing that the highest dose of aducanumab may benefit people with mild cognitive impairment (MCI) and elevated amounts of a protein called amyloid in the brain. That presentation represented an about-face for the company, which had pulled the plug on two trials of the drug in March.

Yet even the most enthusiastic interpreters of the drugs effects on measures of cognition and function agreed that the benefit to patients was a mild slowing, not a halt, and it was certainly not a cure for Alzheimers disease.

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But we also learned that as aducanumab clears amyloid from the brain, it can cause both microscopic hemorrhages and swelling in the brain, particularly in individuals who have a heightened genetic risk of developing Alzheimers disease dementia.

With these facts in hand, aducanumab becomes a kind of thought experiment. What if we could treat mild cognitive impairment caused by Alzheimers disease with a somewhat effective but costly and risky drug? The answers are discomforting.

For much of the 20th century, America largely ignored dementia. It was widely believed that its most common cause was senility, an extreme stage of aging. That changed in April 1976 with a 1,200-word essay titled The Prevalence and Malignancy of Alzheimer Disease: A Major Killer in the Archives of Neurology. In it, neurologist Robert Katzman argued that older adults with disabling cognitive and behavioral problems did not have senility but had Alzheimers disease, a medical problem in need of the full force of American medicine to diagnose, treat, and ideally prevent.

Nearly half a century later, America hasnt come close to solving the problem of Alzheimers disease and other causes of dementia: We dont have effective treatments and we also dont have an effective physician workforce to prescribe and administer them.

Parsing out age-related cognitive complaints from mild cognitive impairment and explaining that diagnosis is a challenging task. There arent currently enough clinicians skilled to evaluate the millions of older adults with cognitive complaints, care for those with MCI and dementia, and prescribe a costly drug that slows but does not cure Alzheimers disease and poses risks to the very same brain they are trying to treat.

Imagine that the FDA approves aducanumab, or a drug like it. Individuals with mild memory problems who dont have MCI should be sent home with reassurance or with treatments for the problems causing their memory complaints, such as anxiety, too much alcohol, or poor sleep. Those with MCI thats about 15% of older Americans would be candidates for PET scans to measure the amount of amyloid in the brain.

To evaluate the millions of Americans who see a doctor because my memory isnt as good as it used to be, overworked and underskilled clinicians are likely to take shortcuts: Never mind diagnosing mild cognitive impairment. Just order the amyloid test. If its positive, prescribe the drug. Otherwise, dont prescribe it.

That approach will be costly. A PET scan for brain amyloid costs around $4,000. Less-costly spinal fluid tests could substitute, but few clinicians are skilled at performing them. Aducanumab, as a manufactured and injected monoclonal antibody, will be expensive. The risk of small swellings and bleeds in the brain would require MRIs to assess safety, which would increase the need for clinicians skilled in interpreting the scans and adjusting treatment plans.

A drug like aducanumab presents clinicians with other novel challenges. It is one of several drugs whose risks, and possibly its benefits as well, are associated with having the ApoE4 gene a gene known to increase an individuals lifetime risk of developing Alzheimers disease dementia. The decision to start the drug may well include ApoE testing so individuals can better understand their risks and possibly responses to the drug.

Genetic testing means that clinicians will have to practice genetic counseling at visits that may need to expand from the dyad of patient and caregiver to include an extended and worried family. A prescription for aducanumab would be startling news for a patients siblings, adult children, and grandchildren: You too may have the Alzheimers gene. You too may want to have an amyloid test.

A treatment that slows Alzheimers disease, that delays the onset of dementia, promises to reduce disability and preserve autonomy. The failure to properly prescribe it could, however, increase the spectacular tallies of the time and costs of caregiving that define much of the Alzheimers crisis.

Lets assume that additional studies show that aducanumab does indeed slow the progression of Alzheimers disease with benefits that exceed its risks. Some of those who take the drug will die of other causes, such as heart disease or cancer, before dementia takes hold. But others will, in time, experience more and more disabling cognitive impairments. As they do, theyll need care.

Some will be cared for in nursing homes or facilities devoted to dementia care. Most will be cared for at home. The Alzheimers Association estimates that in 2018, 16.3 million family members and friends provided 18.5 billion hours of unpaid care to people with Alzheimers and other dementias.

This care ought to include education and training for patients and caregivers. It should also include activity programs tailored to patients abilities and disabilities. These include memory cafs, where people come together not as patients but persons, and centers whose staff members are skilled at creating days that are safe, social, and engaging, with activities such as reminiscence, music, theater, art, and exercise.

Although these ought to be the standard of care, few of them are routinely available to caregivers and patients. Doctors dont typically prescribe them, and their costs are mostly paid out of pocket. A 2013 report estimated that these out-of-pocket costs, together with the time caregivers devote to care, make up as much as half of the diseases annual $200 billion-plus cost.

A disease-slowing treatment that reduces disability ought to reduce the time spent on caregiving. But it will not allow the U.S. to ignore its fractured and disorganized system of dementia care and how this nonsystem offloads much of the costs onto patients and families. Medicare, which was created in 1965, does not pay for long-term care. We must update this antiquated law and support long-term care.

The ability to control Alzheimers disease with a drug will also demand that we engage with difficult issues regarding life and death. Disease-slowing treatments for Alzheimers will challenge our criteria for access to hospice care, as well as to physician aid in dying. Individuals with a chronic and progressive disease like Alzheimers may, in time, decide they no longer want treatment. A robust ethic of respect for persons supports their right to stop treatment. It is entirely possible that some patients, as they decline, may decide: Enough. This disease has progressed. I want to stop treatment.

After that decision or if the drug doesnt work what kind of palliative care is available when death is not in six months away but may be six years away, or longer? Medicares hospice benefit is available only to individuals with six months or fewer to live.

Physician aid in dying, which is available to residents of nine states and the District of Columbia, is also not an option. Individuals who choose this route must have a prognosis of living six months or fewer, be able to decide to end their life, and be able to take the lethal dose of medication.

We ought to be deeply concerned that the limited access to care and its cost are not perverse incentives to seek aid in dying.

We should also expect that the more we control the natural history of Alzheimers disease, the more well begin to question when were dying of it and how we should die.

Katzman foreshadowed this in closing his 1976 essay: In focusing attention on the mortality associated with Alzheimer disease, our goal is not to prolong the lives of severely demented persons, but rather to call attention to a disease whose etiology must be determined, whose course must be aborted, and ultimately a disease to be prevented.

In 2012, the National Plan to Address Alzheimers Disease premiered a strategy to achieve Katzmans vision. Goal number one was that by 2025 we will prevent and effectively treat the disease. Research on aducanumab and other drugs in the pipeline that target amyloid and other causes of neurodegeneration is one route to achieving this. Equally important is disseminating strategies that promote brain health exercise, education, smoking cessation, and the like that have been decreasing the risk of developing dementia since the 1970s.

We do this research with hope that drug interventions will help address the economic and moral costs that have transformed Alzheimers from Katzmans common disease into a crisis. At the same time, we must be mindful that these interventions will present new economic and moral costs. If we fail to address them, the crisis will endure.

Jason Karlawish, M.D., is co-director of the Penn Memory Center and a site investigator for clinical trials sponsored jointly by the National Institute on Aging and Novartis (Generations program) and the NIA and Eli Lilly (the A4 Study). You can follow him on twitter @jasonkarlawish.

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Aducanumab isn't the simple solution to the Alzheimer's crisis - STAT - STAT

By TNH Staff December 21, 2019

Dr. Steven Kalkanis, CEO of the Henry Ford Medical Group. (Photo: Courtesy of the Henry Ford Medical Group)

DETROIT, MI On December 19, the nationally-recognized Henry Ford Health System announced the selection of world-renowned neurosurgeon Dr. Steven Kalkanis as Chief Executive Officer of the Henry Ford Medical Group.

The text of the news release follows:

Following an extensive national search, Henry Ford Health System has selected its own Dr. Steven N. Kalkanis, to be the Chief Executive Officer of the Henry Ford Medical Group (HFMG), effective Jan. 1, 2020. He succeeds Dr. William A. Conway who is stepping down after more than four decades with the health system.

Dr. Kalkanis will provide strategic leadership and direction over the 1,900-member group of physicians and researchers, responsible for all aspects of clinical performance across 40 specialties. Additionally, Dr. Kalkanis will also serve as Henry Fords Senior Vice President and Chief Academic Officer, working to advance the health systems academic mission, including the development and advancement of all research and medical education programs.

We are proud to welcome Dr. Steven Kalkanis to this expanded role, said Wright L. Lassiter, III, President and CEO, Henry Ford Health System. Not only is Steve an accomplished and recognized neurosurgeon, he is a transformational leader who can build on the strong history and tradition of the Henry Ford Medical Group. We are excited to partner with him to drive the innovative approaches for which this medical group has long been known.

Dr. Kalkanis will also work collaboratively with health system clinical and operational leaders, as well as national and community partners to provide exceptional patient care and advance the health systems population health and accountable care strategies. Dr. Adnan Munkarah, Henry Ford Health Systems Executive Vice President and Chief Clinical Officer, said Dr. Kalkanis brings the kind of dynamic leadership that will help Henry Ford maintain its leading role in this area. Creating meaningful solutions for our patients and members that provide the most advanced, innovative, highest quality and safest care at the lowest possible cost cannot be done without strong, committed leadership and trusted partners. Steve is a truly collaborative leader who always acts in the best interests of his patients and their families, as well as his colleagues. We are confident that he can build critical partnerships both inside and outside our organization as we work to achieve lasting health and wellness in the communities we serve.

Dr. Kalkanis joined Henry Ford in 2004 and is currently the Chair of the health systems Department of Neurosurgery, ranked among the nations best by U.S. News and World Report. He is also the Medical Director of the Henry Ford Cancer Institute, leading the expansion of cancer care services across the system, including the spearheading of a comprehensive precision medicine and molecular tumor board program for all cancer types, and the development of the health systems new destination cancer facility, expected to open in 2020.

I am honored to follow in the footsteps of such a storied and respected leader of the Henry Ford Medical Group, said Dr. Kalkanis. To have the opportunity to be part of a compassionate and diverse culture that is relentless in its pursuit of clinical innovation, pioneering research and next generation medical education has been a privilege. In this new capacity, I am more committed than ever to stewarding transformational healthcare through a combination of precision medicine and digital advancements, distinctly personalized care, value-based solutions and a dedication to addressing the real challenges in our communities.

An internationally recognized brain tumor expert, Dr. Kalkanis currently serves as President of the Congress of Neurological Surgeons (CNS), the largest association of its kind. In 2018, he was also named a Director of the American Board of Neurological Surgery, the official accrediting and credentialing body for all neurosurgeons practicing in the U.S. Actively involved in clinical trials and research, he leads a translational research laboratory investigating the molecular genetic differences between short and long term brain tumor survivors with the goal of refining future personalized medicine treatment protocols. He has also served as a visiting professor and guest lecturer for more than 100 national and international audiences and has authored more than 150 peer-reviewed publications.

A metro Detroit native, Dr. Kalkanis completed his neurosurgical training at Massachusetts General Hospital in Boston. He is a graduate of both Harvard University and Harvard Medical School.

More information about the HFMG is available online: https://www.henryford.com/about/hfmg.

Original post:
Dr. Steven Kalkanis Selected as CEO of Henry Ford Medical Group - The National Herald

NEW YORK and CLEVELAND, Dec. 20, 2019 (GLOBE NEWSWIRE) -- Abeona Therapeutics Inc. (Nasdaq: ABEO), a fully-integrated leader in gene and cell therapy, today announced that the European Medicines Agency (EMA) has granted Priority Medicines (PRIME) designation to the Companys ABO-102 program studying its adeno-associated virus 9 (AAV9) gene therapy for Sanfilippo syndrome type A (MPS IIIA). The PRIME designation is based on nonclinical data and clinical data from the Transpher A Study, a global Phase 1/2 clinical trial evaluating a single-dose of ABO-102 for the treatment of children with MPS IIIA.

EMAs PRIME designation for the ABO-102 program recognizes the urgent need for a treatment option for children suffering from MPS IIIA, and underscores the potential of ABO-102 to modify the course of this devastating lysosomal storage disease, said Joo Siffert, M.D., Chief Executive Officer.

The Transpher A Study is enrolling patients at sites in the U.S., Spain, and Australia. Additional information about the trial is available at AbeonaTrials.com and ClinicalTrials.gov (NCT02716246).

The PRIME initiative provides access to enhanced support for the development of medicines targeting an unmet medical need. The designation affords sponsors with enhanced interaction and early dialogue regarding promising medicines, as well as the possibility of accelerated assessment of medicines applications. PRIME is intended to optimize development plans and speed up evaluation so these medicines can help patients to benefit as early as possible from therapies that may significantly improve their quality of life.

About ABO-102ABO-102 is a novel gene therapy in Phase 1/2 development for Sanfilippo syndrome type A (MPS IIIA), a rare lysosomal storage disease with no approved treatment that primarily affects the central nervous system (CNS). ABO-102 is dosed in a one-time intravenous infusion using an AAV9 vector to deliver a functional copy of the SGSH gene to cells of the CNS and peripheral organs. The therapy is designed to address the underlying SGSH enzyme deficiency responsible for abnormal accumulation of glycosaminoglycans in the brain and throughout the body that results in progressive cell damage and neurodevelopmental and physical decline. In the U.S., Abeona holds Regenerative Medicine Advanced Therapy, Fast Track, Rare Pediatric Disease, and Orphan Drug designations for the ABO-102 clinical program. In the EU, the Company holds PRIME and Orphan medicinal product designations.

About The Transpher A StudyThe Transpher A Study (NCT02716246) is an ongoing, two-year, open-label, dose-escalation, Phase 1/2 global clinical trial assessing ABO-102 for the treatment of patients with Sanfilippo syndrome type A (MPS IIIA). The study, also known as ABT-001, is intended for patients 6 months to 2 years of age and patients older than 2 years with a cognitive Developmental Quotient of 60% or above. The study has enrolled 14 patients to date across three dose cohorts (N=3, N=3, N=8) and remains open for enrollment. The ABO-102 gene therapy is delivered using AAV9 technology via a single-dose intravenous infusion. The studys primary endpoints are neurodevelopment and safety, with secondary endpoints including behavior evaluations, quality of life, enzyme activity in cerebrospinal fluid (CSF) and plasma, heparan sulfate levels in CSF, plasma and urine, and brain and liver volume.

About Sanfilippo Syndrome Type A (MPS IIIA)Sanfilippo syndrome type A (MPS IIIA) is a rare, fatal lysosomal storage disease with no approved treatment that primarily affects the CNS and is characterized by rapid neurodevelopmental and physical decline. Children with MPS IIIA present with progressive language and cognitive decline and behavioral abnormalities. Other symptoms include sleep problems and frequent ear infections. Additionally, distinctive facial features with thick eyebrows or a unibrow, full lips and excessive body hair for ones age, and liver/spleen enlargement are also present in early childhood. MPS IIIA is caused by genetic mutations that lead to a deficiency in the SGSH enzyme responsible for breaking down glycosaminoglycans, which accumulate in cells throughout the body resulting in rapid health decline associated with the disorder.

About Abeona Therapeutics Abeona Therapeutics Inc. is a clinical-stage biopharmaceutical company developing gene and cell therapies for serious diseases. The Companys clinical programs include EB-101, its autologous, gene-corrected cell therapy for recessive dystrophic epidermolysis bullosa, as well as ABO-102 and ABO-101, novel AAV9-based gene therapies for Sanfilippo syndrome types A and B (MPS IIIA and MPS IIIB), respectively. The Companys portfolio of AAV9-based gene therapies also features ABO-202 and ABO-201 for CLN1 disease and CLN3 disease, respectively. Its preclinical assets include ABO-401, which uses a novel vector from Abeonas AIM AAV capsid platform to address all mutations of cystic fibrosis. Abeona has received numerous regulatory designations from the FDA and EMA for its pipeline candidates, including Regenerative Medicine Advanced Therapy designation for two candidates (EB-101 and ABO-102).

Forward Looking StatementThis press release contains certain statements that are forward-looking within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and that involve risks and uncertainties. These statements include statements regarding the potential of ABO-102 to modify the course of lysosomal storage disease; our pipeline including the therapeutic potential for ABO-202 in the treatment of CLN1; the ability to obtain regulatory marketing approvals; and the Companys goals and objectives. We have attempted to identify forward looking statements by such terminology as may, will, anticipate, believe, estimate, expect, intend, and similar expressions.

Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, numerous risks and uncertainties, including but not limited to: continued interest in our rare disease portfolio, our ability to initiate and enroll patients in clinical trials, the impact of competition, the ability to secure licenses for any technology that may be necessary to commercialize our products, the ability to achieve or obtain necessary regulatory approvals, the impact of changes in the financial markets and global economic conditions, risks associated with data analysis and reporting, and other risks as may be detailed from time to time in the Companys annual reports on Form 10-K and quarterly reports on Form 10-Q and other reports filed by the Company with the Securities and Exchange Commission. The Company undertakes no obligation to revise the forward-looking statements or update them to reflect events or circumstances occurring after the date of this presentation, whether as a result of new information, future developments or otherwise, except as required by the federal securities laws.

Investor Contact:Dan FerryLifeSci Advisors, LLC+1 (617) 535-7746daniel@lifesciadvisors.com

Media Contact:Scott SantiamoDirector, Corporate CommunicationsAbeona Therapeutics+1 (718) 344-5843ssantiamo@abeonatherapeutics.com

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Abeona Therapeutics Receives European Medicines Agency PRIME Designation for ABO-102 Gene Therapy in MPS IIIA - GlobeNewswire

Advances in molecular biology and human genetics, coupled with the completion of the Human Genome Project and the increasing power of quantitative genetics to identify disease susceptibility genes, are contributing to a revolution in the practice of medicine. In the 21st century, practicing physicians will focus more on defining genetically determined disease susceptibility in individual patients. This strategy will be used to prevent, modify, and treat a wide array of common disorders that have unique heritable risk factors such as hypertension, obesity, diabetes, arthrosclerosis, and cancer.

The Division of Genetic Medicine provides an academic environment enabling researchers to explore new relationships between disease susceptibility and human genetics. The Division of Genetic Medicine was established to host both research and clinical research programs focused on the genetic basis of health and disease. Equipped with state-of-the-art research tools and facilities, our faculty members are advancing knowledge of the common genetic determinants of cancer, congenital neuropathies, and heart disease. The Division faculty work jointly with the Vanderbilt-Ingram Cancer Center to support the Hereditary Cancer Clinic for treating patients and families who have an inherited predisposition to various malignancies.

Genetic differences in humans at the molecular level not only contribute to the disease process but also significantly impact an individuals ability to respond optimally to drug therapy. Vanderbilt is a pioneer in precisely identifying genetic differences between patients and making rational treatment decisions at the bedside.

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Genetic Medicine | Department of Medicine

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.

Related

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

Researchers at Baylor College of Medicine report today in the journal Neuron evidence that refutes the link between increased levels of herpes virus and Alzheimers disease. In addition, the researchers provide a new statistical and computational framework for the analysis of large-scale sequencing data.

About 50 million people worldwide are affected by Alzheimers disease, a type of progressive dementia that results in the loss of memory, cognitive abilities and verbal skills, and the numbers are growing rapidly. Currently available medications temporarily ease the symptoms or slow the rate of decline, which maximizes the time patients can live and function independently. However, there are no treatments to halt progression of Alzheimers disease.

Like all types of dementia, Alzheimers disease is characterized by massive death of brain cells, the neurons. Identifying the reason why neurons begin and continue to die in the brains of Alzheimers disease patients is an active area of research, said corresponding author Dr. Zhandong Liu, associate professor of pediatrics at Baylor and the Jan and Dan Duncan Neurological Research Institute at Texas Childrens Hospital.

One theory that has gained traction in the past year is that certain microbial infections, such as those caused by viruses, can trigger Alzheimers disease. A 2018 study reported increased levels of human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) in the postmortem brain tissues of more than 1,000 patients with Alzheimers disease when compared to the brain tissues of healthy-aging subjects or those suffering from a different neurodegenerative condition.

Presence of elevated levels of genetic material of herpes viruses indicated active infections, which were linked to Alzheimers disease. In less than a year, this study generated a flurry of excitement and led to the initiation of several studies to better understand the link between viral infections and Alzheimers disease.

Surprisingly, when co-author Dr. Hyun-Hwan Jeong, a postdoctoral fellow in Dr. Lius group and others, reanalyzed the data sets from the 2018 study using the identical statistical methods with rigorous filtering, as well as four commonly used statistical tools, they were unable to produce the same results.

The team was motivated to reanalyze the data from the previous study because they observed that while the p-values (a statistical parameter that predicts the probability of obtaining the observed results of a test, assuming that other conditions are correct) were highly significant, they were being ascribed to data in which the differences were not visually appreciable.

Moreover, the p-values did not fit with simple logistic regression a statistical analysis that predicts the outcome of the data as one of two defined states. In fact, after several types of rigorous statistical tests, they found no link between the abundance of herpes viral DNA or RNA and likelihood of Alzheimers disease in this cohort.

As high-throughput omics technologies, which include those for genomics, proteomics, metabolomics and others, become affordable and easily available, there is a rising trend toward big data in basic biomedical research. In these situations, given the massive amounts of data that have to be mined and extracted in a short time, researchers may be tempted to rely solely on p-values to interpret results and arrive at conclusions, Liu said.

Our study highlights one of the potential pitfalls of over-reliance on p-values. While p-values are a very valuable statistical parameter, they cannot be used as a stand-alone measure of statistical correlation data sets from high-throughput procedures still need to be carefully plotted to visualize the spread of the data, Jeong said. Data sets also have to be used in conjunction with accurately calculated p-values to make gene-disease associations that are statistically correct and biologically meaningful.

Our goal in pursuing and publishing this study was to generate tools and guidelines for big data analysis, so the scientific community can identify treatment strategies that will likely benefit patients, Liu said.

This study was funded by the Huffington Foundation.

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Link between herpes virus infections, Alzheimer's refuted - Baylor College of Medicine News

Drug Target Review lists its 10 most popular news stories from 2019, summarising the drug targets that you wanted to read about.

Drug Target Review has published a wide range of news stories this year, from the identification of novel drug targets to improvements in toxicology studies and developments in screening.

As the year draws to a close, we reflect on the biggest and most popular stories from 2019. To read the full pieces, click on the title of each news story.

A genetic analysis study revealed that variants of hundreds of genes work together in contributing to the development of Tourettes syndrome, in our tenth most popular story this year.

According to the researchers, from the Massachusetts General Hospital (MGH) and collaborators, their findings confirm that the underlying basis for Tourettes syndrome is polygenic, meaning that hundreds of small DNA changes cause the condition, rather than one inactive gene.

The scientists said their next step is to expand their sample size to around 12,000 patients, made possible with a potential international collaboration.

The study was published in the American Journal of Psychiatry.

A group of researchers identified new genetic targets on which BRCA2-driven cancer cells are dependent upon, providing a potential avenue for drug development.

The study, conducted at Brigham and Womens Hospital, used CRISPR and short-hairpin RNAs (shRNAs) to test 380 genes with a known or suspected role in DNA-damage response. This allowed the team to narrow in on the most promising genes: APEX2 and FEN1, two novel targets for breast cancer.

The results were published in Molecular Cell.

Immunotherapy treatment could reduce the persistence of HIV in patients receiving triple therapy, found a group of researchers.

The researchers, from the University of Montreal Hospital Research Centre, discovered that these therapies expose the virus to the immune system. Three proteins PD-1, LAG-3 and TIGIT were uncovered by the scientists as frequently expressed on the surface of HIV-hiding cells; these proteins are also cancer targets.

According to the team, their study could lead to the development of new HIV therapies based on cancer immunotherapies.

The study was published in Nature Communications.

Researchers at the Indiana University School of Medicine developed a blood test to measure pain and improve diagnosis. The team analysed hundreds of patient samples to reveal biomarkers in their blood, which could be used as a scale to determine pain.

According to the researchers, the biomarkers act like a signature that can be matched against a prescription database. This could allow medical professionals to select the appropriate compound and reduce pain for the patient.

The study was published in Molecular Psychiatry.

A team of scientists revealed that immune cells could be key in causing endometriosis, a pelvic pain experienced by women, through an investigation into macrophages. The study was led by researchers from Warwick Medical School and the University of Warwick.

Macrophages can adapt their function according to local signals from their surroundings and so become modified by disease. This led the researchers to add modified macrophages to a cell culture, which resulted in the production of higher levels of insulin-like growth factor-1 (IGF-1).

The team conclude that macrophages therefore present a drug target for endometriosis.

The results can be found in The FASEB Journal.

Scientists from the University of Pennsylvania imaged a molecule that induces inflammation and leads to lupus, in our fifth most popular story of 2019. The researchers discovered that the molecule is comprised of two sections: SHMT2 and BRISC, a cluster of proteins. When these two sections bind to each other, they cause inflammation.

When mice models lacking BRISC were tested, they were resistant to lupus. This led the team to conclude that a molecule which blocks BRISC and SHMT2 could be a drug target for lupus.

The findings were published in Nature.

A team of researchers reported that a CRISPR-Cas9 gene therapy which specifically reduces fat tissue and obesity-related metabolic disease was successful in mice.

The scientists, from Hanyang University, argue that their technique could be used as a way to combat type 2 diabetes and other obesity-related diseases.

Targeting Fabp4, a fatty acid metabolism gene, the researchers observed a 20 percent reduction of body weight in obese mice. It also resulted in improved insulin resistance after only six weeks of treatment.

The findings were published in Genome Research.

A compound that promotes the rebuilding of the protective sheath around nerve cells has been developed by researchers at the Oregon Health & Science University (OHSU).

The team found that the S3 compound reverses the effect of hyaluronic acid (HA) in mice. HA has been found to accumulate in the brain of patients with multiple sclerosis, and accumulation of HA

has also been linked to maturity failure of cells called oligodendrocytes, which generate myelin, the protective layer of axons.

The team therefore believe that the S3 compound could provide a therapeutic strategy for treating nervous system disorders.

The study can be found in Glia.

A group of researchers formed a complex view of the functional dysbiosis in the gut microbiome during inflammatory bowel disease (IBD), to reveal new targets for treatments.

The scientists, from theBroad InstituteofMITandHarvard University, observed microbial changes and human gene regulatory shifts from stool and blood samples of patients.

This multi-omic study enabled the team to discover that during periods of disease activity, IBD patients had higher levels of polyunsaturated fatty acids in both the blood and stool. They also identified other varying levels of nutrients and vitamins, presenting several potential drug targets.

The findings were published in Nature.

In our most popular news piece this year, researchers found that the small molecule PJ34 reduces the number of human pancreatic cancer cells in transplanted tumours by 90 percent.

The team, from Tel Aviv University, built on previous research to treat xenografts with their small molecule. It is permeable in the cell membrane, but affects human cancer cells exclusively, making it an attractive compound for development.

The scientists found that PJ34 causes a rapid cell death and in one mouse, the tumour completely disappeared. They concluded that the molecule could be a potent therapeutic against pancreatic cancer.

The results were published in Oncotarget.

Related organisationsBrigham and Women's Hospital, Hanyang University, Harvard University, Indiana University School of Medicine, Massachusetts General Hospital (MGH), MIT, Oregon Health & Science University (OHSU), Pennsylvania University, Tel Aviv University, University of Montreal Hospital Research Centre, Warwick Medical School, Warwick University

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DTR's news round-up 2019: the stories that defined the year - Drug Target Review

Spark will continue its operations in Philadelphia as an independent company within the Roche Group

Roche and Spark Therapeutics, Inc. have 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.

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Roche acquires Spark Therapeutics to strengthen presence in gene therapy - BSI bureau

DUBLIN--(BUSINESS WIRE)--The "Innovations Transforming the Global Healthcare IT, Biomarker, Biologics, and Small Molecule Landscape" report has been added to ResearchAndMarkets.com's offering.

This edition of the Life Science, Health & Wellness TechVision Opportunity Engine (TOE) provides technological insights across 26 global healthcare innovations.

The technologies analyzed include advances in digital health, biologics, small molecules, medical imaging, dental caries and precision oncology platforms. The TOE also covers application and megatrends impact, apart from exclusive analyst insights for each innovation.

The Life Science, Health & Wellness TOE will feature disruptive technology advances in the global life sciences industry. The technologies and innovations profiled will encompass developments across genetic engineering, drug discovery and development, biomarkers, tissue engineering, synthetic biology, microbiome, disease management, as well as health and wellness among several other platforms.

The Health & Wellness cluster tracks developments in a myriad of areas including genetic engineering, regenerative medicine, drug discovery and development, nanomedicine, nutrition, cosmetic procedures, pain and disease management and therapies, drug delivery, personalized medicine, and smart healthcare.

Companies featured:

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Innovations Transforming the Global Healthcare IT, Biomarker, Biologics, and Small Molecule Landscape, 2019 Research Report - ResearchAndMarkets.com -...

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

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

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

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

Precision medicine is a growth area

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

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

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

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

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

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

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

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

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

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

Written by

Arthur Hermann, Fellow, Precision Medicine, World Economic Forum

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

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

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

SALT LAKE CITY, Dec. 14, 2019 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, announced that results of a new validation study of the companys polygenic risk score (PRS) for breast cancer were presented at the 2019 San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Tx. The key finding is that the PRS significantly improves the precision and accuracy of breast cancer risk estimates for women of European ancestry who have pathogenic variants (PV) in high- and moderate-penetrance breast cancer genes.

Our goal is to help women understand their risk of breast cancer so that they can take steps to live longer, healthier lives. Women who have a family history of breast cancer should consider hereditary cancer testing with the myRisk Hereditary Cancer test, said Jerry Lanchbury, Ph.D., chief scientific officer of Myriad Genetics. In this landmark study, we demonstrated that for women who test positive for a mutation in one of the five most common breast cancer genes, there are additional genetic factors called single nucleotide polymorphisms (SNPs) that can further influence their lifetime risk of breast cancer.

A summary of the study follows below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with SABCS meeting news and updates by using the #SACBS19 hashtag.

Myriad Poster Presentation Title: Polygenic Breast Cancer Risk Modification in Carriers of High and Intermediate Risk Gene Mutations.Presenter: Elisha Hughes, Ph.D.Date: Saturday, Dec. 14, 2019, 7:009:00 a.m.Location: Poster P6-08-07

This validation study evaluated the 86-SNP PRS as a breast cancer risk factor for women who carry PV in the BRCA1, BRCA2, CHEK2, ATM and PALB2 genes and for PV-free women. The analysis included data from 152,012 women of European ancestry who received a myRisk Hereditary Cancer test as part of their clinical hereditary cancer risk assessment. The results demonstrated that the 86-SNP PRS significantly modified the breast cancer risk for women with pathogenic mutations in the five tested breast cancer genes (p-value <10-4). For some women, the PRS significantly increased the gene-based risk of breast cancer, while in others the gene-based risk was reduced (see Graph 1). Importantly, the greatest PRS risk-modification was observed in carriers of CHEK2, ATM and PALB2 mutations with some women reaching the risk levels associated with BRCA1 and BRCA2 mutations.

To view Graph 1: PRS Significantly Modifies Lifetime Breast Cancer Risk in Mutation Carriers , please visit the following link: https://www.globenewswire.com/NewsRoom/AttachmentNg/d56c93ca-e00f-452d-b051-6325a578454c

These findings mean that we have the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes, said Elisha Hughes, Ph.D., lead investigator and director of Bioinformatics at Myriad Genetics. We are optimistic that this additional genetic information can help clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future.

Next StepsThe company plans to publish these new data in a peer reviewed medical journal and make the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes. The PRS currently is available as part of myRisk Hereditary Cancer enhanced with riskScore for women of European ancestry who test negative for pathogenic mutations in the breast cancer genes. Specifically, the riskScore test combines the PRS with the Tyrer-Cuzick model to estimate a womans 5-year and lifetime risk for developing breast cancer. The company is committed to making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and is developing the test for women of Hispanic and African-American ancestry who test negative. The company is currently conducting the largest ever PRS study in African Americans and will present the data at a future meeting.

Please visit Myriad at booth #113 to learn more about our portfolio of genetic tests for breast cancer. Follow Myriad on Twitter via @myriadgenetics and keep up to date with Symposium news by using the hashtag #SABCS19.

About riskScoreriskScore is a new clinically validated personalized medicine tool that enhances Myriads myRisk Hereditary Cancer test. riskScore helps to further predict a womens lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary CancerThe Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

About Myriad GeneticsMyriad Genetics Inc. is a leading precision medicine company dedicated to being a trusted advisor transforming patient lives worldwide with pioneering molecular diagnostics. Myriad discovers and commercializes molecular diagnostic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across six major medical specialties where molecular diagnostics can significantly improve patient care and lower healthcare costs. Myriad is focused on five critical success factors: building upon a solid hereditary cancer foundation, growing new product volume, expanding reimbursement coverage for new products, increasing RNA kit revenue internationally and improving profitability with Elevate 2020. For more information on how Myriad is making a difference, please visit the Company's website: http://www.myriad.com.

Myriad, the Myriad logo, BART, BRACAnalysis, Colaris, Colaris AP, myPath, myRisk, Myriad myRisk, myRisk Hereditary Cancer, myChoice, myPlan, BRACAnalysis CDx, Tumor BRACAnalysis CDx, myChoice CDx, EndoPredict, Vectra, GeneSight, riskScore, Prolaris, Foresight and Prequel are trademarks or registered trademarks of Myriad Genetics, Inc. or its wholly owned subsidiaries in the United States and foreign countries. MYGN-F, MYGN-G.

Safe Harbor StatementThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995, including statements related to the Companys polygenic risk score and data being featured at the 2019 San Antonio Breast Cancer Symposium being held Dec. 10-14, 2019 in San Antonio, Tx.; the potential to significantly improve the precision of hereditary cancer risk assessment for women who test positive for mutations in the high and intermediate risk breast cancer genes; this additional genetic information helping clinicians more accurately predict the risk of breast cancer and provide the best care for their patients in the future; publishing these new data in a peer reviewed medical journal and making the PRS available for U.S. women of European ancestry who test positive for mutations in breast cancer genes; making myRisk Hereditary Cancer enhanced with riskScore available to all ethnicities and developing the test for women of Hispanic and African-American ancestry who test negative; conducting the largest ever PRS study in African Americans and presenting the data at a future meeting; and the Company's strategic directives under the caption "About Myriad Genetics." These "forward-looking statements" are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by forward-looking statements. These risks and uncertainties include, but are not limited to: the risk that sales and profit margins of our molecular diagnostic tests and pharmaceutical and clinical services may decline; risks related to our ability to transition from our existing product portfolio to our new tests, including unexpected costs and delays; risks related to decisions or changes in governmental or private insurers reimbursement levels for our tests or our ability to obtain reimbursement for our new tests at comparable levels to our existing tests; risks related to increased competition and the development of new competing tests and services; the risk that we may be unable to develop or achieve commercial success for additional molecular diagnostic tests and pharmaceutical and clinical services in a timely manner, or at all; the risk that we may not successfully develop new markets for our molecular diagnostic tests and pharmaceutical and clinical services, including our ability to successfully generate revenue outside the United States; the risk that licenses to the technology underlying our molecular diagnostic tests and pharmaceutical and clinical services and any future tests and services are terminated or cannot be maintained on satisfactory terms; risks related to delays or other problems with operating our laboratory testing facilities and our healthcare clinic; risks related to public concern over genetic testing in general or our tests in particular; risks related to regulatory requirements or enforcement in the United States and foreign countries and changes in the structure of the healthcare system or healthcare payment systems; risks related to our ability to obtain new corporate collaborations or licenses and acquire new technologies or businesses on satisfactory terms, if at all; risks related to our ability to successfully integrate and derive benefits from any technologies or businesses that we license or acquire; risks related to our projections about our business, results of operations and financial condition; risks related to the potential market opportunity for our products and services; the risk that we or our licensors may be unable to protect or that third parties will infringe the proprietary technologies underlying our tests; the risk of patent-infringement claims or challenges to the validity of our patents or other intellectual property; risks related to changes in intellectual property laws covering our molecular diagnostic tests and pharmaceutical and clinical services and patents or enforcement in the United States and foreign countries, such as the Supreme Court decision in the lawsuit brought against us by the Association for Molecular Pathology et al; risks of new, changing and competitive technologies and regulations in the United States and internationally; the risk that we may be unable to comply with financial operating covenants under our credit or lending agreements; the risk that we will be unable to pay, when due, amounts due under our credit or lending agreements; and other factors discussed under the heading "Risk Factors" contained in Item 1A of our most recent Annual Report on Form 10-K for the fiscal year ended June 30, 2019, which has been filed with the Securities and Exchange Commission, as well as any updates to those risk factors filed from time to time in our Quarterly Reports on Form 10-Q or Current Reports on Form 8-K. All information in this press release is as of the date of the release, and Myriad undertakes no duty to update this information unless required by law.

Graph 1

PRS Significantly Modifies Lifetime Breast Cancer Risk in Mutation Carriers

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Myriad's Polygenic Risk Score Personalizes Risk of Breast Cancer for Woman with a Genetic Mutation in Important Breast Cancer GenesNew Clinical...

IU School of Medicine 12/13/19

SAN ANTONIOIndiana University School of Medicine researchers have discovered how to predict whether triple negative breast cancer will recur,and whichwomenare likely toremain disease-free. They will present their findingson December 13, 2019,at the San Antonio Breast Cancer Symposium, the most influential gathering of breast cancer researchers and physicians in the world.

Milan Radovich, PhD, andBryan Schneider, MD,discovered that women whose plasmacontained genetic material from a tumor referred to as circulating tumor DNA had only a 56 percent chance of being cancer-free two years following chemotherapy and surgery. Patients who did not have circulating tumor DNA, or ctDNA,in their plasma had an 81 percent chance that the cancer would not return after the same amount of time.

Triple negative breast cancer is one of the most aggressive and deadliest types of breast cancer because it lacks common traits used to diagnose and treat most other breast cancers. Developing cures for the disease is a priority of theIU Precision Health Initiative Grand Challenge.

The study also examined the impact of circulating tumor cells,or CTCs,which arelive tumor cells that are released from tumors somewhere in the body and float in the blood.

What we found is that if patientswerenegative for bothctDNA and CTC, 90 percent of the women with triple negative breast cancer remained cancer-free after two years, said Radovich, who is lead author of this study and associate professor of surgery and medicalandmolecular genetics at IU School of Medicine.

Advocates for breast cancer researchsaythey are excited to hear about these results.

The implications of this discovery will change the lives of thousands of breast cancer patients, saidNadia E.Miller,who is a breast cancer survivor andpresident of Pink-4-Ever, which is a breast cancer advocacy group in Indianapolis. This is a huge leap toward more favorable outcomes and interventions for triple negative breast cancer patients. To provide physicians with more information to improve the lives of somany is encouraging!

Radovich and Schneider are researchers in theIndiana University Melvin and Bren Simon Cancer Centerand theVera Bradley Foundation Center for Breast Cancer Research. They lead the Precision Health Initiatives triple negative breast cancer team.

The researchers, along with colleagues from theHoosier Cancer Research Network, analyzed plasma samples taken from the blood of 142 women with triple negative breast cancer who had undergone chemotherapy prior to surgery. Utilizing theFoundationOne Liquid Test, circulating tumor DNA was identified in 90 of the women;52 were negative.

The women were participants inBRE12-158,a clinical study that testedgenomically directed therapyversus treatment of the physicians choicein patients withstageI,II or IIItriple negative breast cancer.

Detection of circulatingtumorDNA was also associated with poor overall survival. Specifically, the study showed that patients withcirculatingtumorDNA were four times more likely to die from the disease when compared to those who tested negative for it.

The authors say the next step is a new clinical study expected to begin in early 2020, which utilizes this discovery to enroll patients who are at high risk for recurrence and evaluates new treatment options for them.

Just telling a patient they are at high risk for reoccurrence isnt overly helpful unless you can act on it, said Schneider, who is senior author of this study and Vera Bradley Professor of Oncologyat IU School of Medicine. Whats more important is the ability to act on that in a way to improve outcomes.

Organizers of theSan Antonio Breast Cancer Symposiumselected the researchto highlight frommore than2,000 scientific submissions.

This study was funded by the Vera Bradley Foundation for Breast Cancerand the Walther Cancer Foundation.It is part of theIndiana University Precision Health InitiativeGrand Challenge.The study was managed by the Hoosier Cancer Research Network and enrolled at 22clinical sites across theUnited States.

To interviewMilan Radovich or Bryan P. Schneideron Friday, Dec. 13,contactChristine Drury at 317-385-9227 (cell)on-site in San Antonio.

Local mediacancontact Anna Carrera in Indianapolisat 614-570-6503 (cell).

For the full media kit, click here.

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What theyre saying:

IU School of Medicine DeanJayL.Hess, MD, PhD, MHSA:While we have made extraordinary progress in treating many types of breast cancer, triple negative disease remains a formidable challenge. We are dedicating substantial expertise and resources to this disease, and this discovery is an important step forward. We will continue to press ahead until we have new therapies to offer women with this most aggressive form of breast cancer.

IU School of Medicine Executive Associate Dean for ResearchAnanthaShekhar, MD, PhD:I could not be more proud of our research team here at IU School of Medicine and the IU Precision Health InitiativeGrand Challenge. A few years ago, I gave the teams the challenge to come up with targeted treatments, cures and preventions for triple negative breast cancer, where there had been none. The findings, announced today, show we are well on our way to achieving these bold goals.

Indiana University Melvin and Bren Simon Cancer Center DirectorPatrick J. Loehrer, MD:Addressing an issue of importance in Indiana and globally, our IU cancer researchers are making novel discoveries that have the real potential to impact women with triple negative breast cancer. This work does not happen in a vacuum, but is a product of team science, which characterizes the fabric of our National Cancer Institute-designated Comprehensive Cancer Center.

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IU School of Medicine is the largest medical school in the U.S. and is annually ranked among the top medical schools in the nation by U.S. News & World Report. The school offers high-quality medical education, access to leading medical research and rich campus life in nine Indiana cities, including rural and urban locations consistently recognized for livability.

The Precision Health Initiative is IUs big health care solution. Led by the IU School of Medicine, the Precision Health Initiative team is working to prevent and cure diseases through a more precise understanding of the genetic, behavioral, and environmental factors that influence a persons health, with bold goals to cure one cancer and one childhood disease and to prevent one chronic illness and one neurodegenerative disease.

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Indiana University School of Medicine researchers use cutting-edge technology to predict which triple negative breast cancer patients may avoid...