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Archive for the ‘Genetic medicine’ Category

Genetic counseling program helps patients take control of their health – Medical University of South Carolina

Thursday, June 24th, 2021

Mary Katherine Melroy, 40, was relieved when a mammogram in November 2020 determined that the lump she found in her breast wasnt a cause for concern. What was concerning, however, was her risk assessment score for developing breast cancer.

She was referred to the High-Risk Breast Evaluation Clinicat MUSC Hollings Cancer Center, where she met with a genetic counselor and completed testing to search for clues that may have put her at a greater risk of developing an inherited form of breast cancer. Thats when she learned she had a pathogenic mutation in the CHEK2 gene and a 25% to 39% chance of developing breast cancer in her lifetime more than double the risk of the average U.S. woman. The mutation also increases her risk of developing colon and thyroid cancer.

Instead of panicking, Melroy was comforted by the news. It gave her the answers shed been searching for when her mom was diagnosed with breast cancer 10 years ago at the age of 58.

It was actually a relief because it made sense, said Melroy, who never understood how breast cancer could affect someone as petite, healthy and fit as her mom. It didnt give me anxiety to know I had this mutation. It put the ball in my court to do what I need to do.

Melroy got to work researching her mutation and learned that opting to have a bilateral mastectomy a surgery used to remove both breasts could reduce her risk of breast cancer to 5%. After watching her mom struggle with the side effects of chemotherapy, she decided she wanted to do everything in her power to reduce her risk of going through the same thing. She plans to get the surgery toward the end of 2021.

Knowing shes at increased risk of cancer is empowering for Melroy, as she feels like she has options for shaping her future.

As an adult, there are very few things that I feel like I can control, but this is a piece of the puzzle of my health that I can take control of. Id rather get the surgery than go in for screenings twice a year because Id feel like we were just waiting until we found something, said Melroy, who also plans to talk with her doctor about getting screened early for colon cancer.

Theres so much you can do when you have the knowledge. A lot of people are scared at the thought of getting genetic testing, but whats scary to me is looking at what happened to my mom.

At Hollings, the demand for genetic testing has risen 422% in the last year. In response, the genetic counseling program is the largest it has ever been, employing six counselors total, two of whom provide full-time onsite services for Hollings patients.

While genetic testings popularity took off in 2013 following a Supreme Court case that allowed more than one company to test for certain genetic mutations, it continues to become more common as testing guidelines expand to include more people. Its now recommended that all pancreatic, ovarian and high-risk prostate cancer patients be referred for testing, and talks of including all breast cancer patients are in the works.

According to Libby Malphrus, one of Hollings onsite counselors, the ability of Hollings program to grow with the demand is one thing that makes it unique.

Theres a shortage of genetic counselors nationally. The access people have to genetic counselors at Hollings is huge and something most large health care systems strive for, said Malphrus. We have a multitude of counselors and various ways in which we can deliver that service, including through telemedicine, and thats a huge asset.

Because the program is still growing, genetic counseling currently is only available to current cancer patients or those deemed at high risk of developing cancer based on their family history. For patients who already have cancer, genetic testing can help to inform their treatment plans, from determining which surgical techniques should be used to how aggressively the cancer should be treated.

It can also determine whether theyre at risk of developing other cancer types and whether their family members may need increased surveillance.

While the information found can potentially be lifesaving for cancer patients and their families, Charly Harris, the programs other full-time genetic counselor, reminds patients that testing also comes with risks.

When someone is diagnosed with cancer, they dont want to think about whether there are other cancer types for which they may be at risk. Their diagnosis is often already a big surprise for them, so adding additional cancer risks can be too much information in that moment, said Harris, who noted Hollings counselors meet with patients prior to testing to discuss the pros and cons.

Malphrus added, Its hard enough for individuals to battle their diagnoses and watch the emotional impact that has on their families without the thought that they could be passing that gene on to their children. Thats heavy information, which is why we dont want anyone to assume they should be tested just because they have cancer.

Melroy understands the information found through her testing affects not only her own health but the health of her sisters, brother and children. Shes already planning on having her 6-year-old daughter tested when shes old enough.

While the technology used in genetic testing continues to grow in speed and efficiency, Malphrus and Harris acknowledge theres still a lot that is unknown about how to use the results. Finding a mutation by testing more genes isnt helpful if counselors dont know what that mutation means.

Thats why its important for patients to have testing done through a genetic counselor who is trained in medical genetic testing as opposed to companies offering direct-to-consumer DNA testing. Direct-to-consumer tests only examine a small number of genes, giving an incomplete picture of potential health risks. The test at Hollings examines up to 84 genes that are known to be associated with an increased cancer risk.

While certain cancers, like breast and ovarian, are more strongly associated with hereditary factors than others, most cancers are not inherited. In fact, only 5% to 10% of breast cancers and 20% to 25% of ovarian cancers are hereditary, which is why getting regular cancer screenings is important regardless of genetic testing results.

People often think, I dont have a family history, so its not going to happen to me, said Harris. I always remind my patients that they still have the general population risk of all cancers. Just because weve lowered the risk for hereditary cancers doesnt mean they dont need to continue getting screened.

Individuals can lower their cancer risks through lifestyle choices such as maintaining a healthy weight and diet, getting regular exercise, avoiding smoking and staying on top of their preventive care. Additionally, getting the HPV vaccine can protect against six types of cancers.

While Harris and Malphrus both entered genetic counseling due to their love of the science, they agree that the most rewarding part of their job is giving patients a sense of control over something they often feel they cant change.

Genetics is complicated, and its only becoming more complex, said Malphrus. Its rewarding to be that bridge between science and medicine and to help people to make educated choices that are best for themselves and their families.

Originally posted here:
Genetic counseling program helps patients take control of their health - Medical University of South Carolina


One-year-old baby in UAE receives imported genetic medicine to treat rare disease – Gulf News

Thursday, June 24th, 2021

A one-year-old Emirati baby Afra with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration. Image Credit:

Abu Dhabi: A one-year-old Emirati baby with a progressive muscular disease has been successfully treated with an advanced genetic treatment that will prevent further deterioration.

Baby Afra was diagnosed with spinal muscular atrophy (SMA), an inherited disease that damages nerve cells, called motor neurons, in the spinal cord. The most common form of the rare neuromuscular disease involves an abnormal or missing survival motor neuron 1 gene (SMN1 gene).

I first noticed abnormal movements in Afra when she was only three months old and quickly consulted a paediatric physician. After multiple tests, Afra was diagnosed with SMA, and transferred to the Sheikh Khalifa Medical City (SKMC), said Afras mother said.

Genetic medicine

The SKMC medical team sprang into action and developed a comprehensive treatment plan to prevent further deterioration. This included importing a genetic medicine, which has viral vectors that target the affected neurons, inserting copies of normal SMN1 genes inside. Following this, the muscle condition improves in terms of movement and function.

Afras journey towards recovery is a significant achievement, not just for the A u Dhabi Health Services Company (Seha) network [which includes SKMC], but for the wider healthcare ecosystem in the country, as we provide hope and create impact for families with children diagnosed with SMA, said Dr Mariam Al Mazrouei, SKMC chief executive director.

Early intervention

The key to successfully overcoming SMA is early diagnosis and implementation of a vigorous treatment strategy. This keeps the neurons as intact as possible and prevents further damage, said Dr Omar Ismail, paediatric neurology consultant and head of paediatric neurology at the hospital.

In Afras case, even though she was brought in quite late with affected limbs, we quickly jumped into action with an inclusive treatment plan that prevented further deterioration of her muscles while we waited for the required genetic treatment to arrive from abroad. This particularly helped with Afras breathing muscles, and eliminated the need for an artificial respiratory device, Dr Ismail said.

Baby Afra will continue to be followed up by doctors at SKMC.

The medical team has implemented a robust treatment plan. I am tremendously grateful to them for their diligence in treating my daughter, Afras mother said.


According to the Centre for Arab Genomic Studies, the prevalence of SMA in GCC populations is thought to be at least 50 times higher than in the United States, with more than 50 cases per 100,000 live births, compared to only 1.2 in the United States. It is one of the diseases that the Abu Dhabi Emirates Premarital Screening and Counselling Programme screens for, before couples wed, in order to alert couples about possible risk.

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One-year-old baby in UAE receives imported genetic medicine to treat rare disease - Gulf News


Black and non-Hispanic White Women Found to Have No Differences in Genetic Risk for Breast Cancer – Cancer Network

Thursday, June 24th, 2021

The findings challenge past, smaller studies that found Black women face a greater genetic risk [for breast cancer] and the suggestion that race should be an independent factor when considering genetic testing, said first authorSusan Domchek, MD,executive director of the Basser Center for BRCA.2

Investigators studied 3946 Black and 25278 non-Hispanic White women, with 5.6% and 5.06%, respectively, found to have 1 of 12 genes linked to breast cancer. The study looked at the main PVs in genes, tumor estrogen receptor (ER) status, and age.

PVs in 3 different genesCHEK2, BRCA2, and PALB2were found to be the most statistically different between the two races. For CHEK2, non-Hispanic White women were more likely to have PVs than Black women (1.29% vs 0.38%; P < .001). For BRCA2, Black women were more likely to have PVs than non-Hispanic White women (1.80% vs 1.24%; P = .005); in PALB2, more PVs were noted in Black women (1.01% vs 0.40%; P < .001).

In ER-positive breast cancer, Black women were more likely to have BRCA2 (1.56% vs 1.05%; P = .04) and were less likely to have CHEK2 (0.46% vs 1.36%; P < .001) PVs compared with white women. There was a higher prevalence of PALB2 PVs in Black vs non-Hispanic women with ER-negative breast cancer (1.83% vs 0.95%; P = .04) and triple-negative breast cancer (2.79% vs 1.23%; P = .05). BRCA1, BRCA2, and PALB2 accounted for 75% of PVs in ER-negative cases, at rates of 81.3% in Black women and 77.0% in non-Hispanic White women.

The investigators found that there was no difference in rates of PVs by age of diagnosis before 50 years (8.83% of Black vs 10.04% of non-Hispanic White women; P = .25). CHEK2 was more likely to occur in non-Hispanic White women than Black women diagnosed under the age of 50 (1.82 vs 0.43; P <.001). Adjusting for age, it was found the prevalence ration was 1.08 for the comparison of non-Hispanic and Black women (1.08; 95% CI, 1.02-1.14). In PALB2, there was a higher standardized prevalence ratio for PVs in Black women (.40; 95% CI, 0.33-0.38) whereas CHEK2 had a lower prevalence (3.35; 95% CI, 3.01-3.74) by age.

After age adjustment, there was no longer a prevalence difference found for BRCA2, with a standardized ratio of 0.91 (95% CI, 0.81-1.01). Notably, 4 PVs of ATM, BRCA1, RAD51D, and TP53 showed significant association with ethnicity when age was adjusted, whereas no such correlation was seen previously.

Investigators noted that one limitation of this study was unknown family history of patients. They also had a very small group of patients with RAD51C and RAD51D to be able to draw conclusions about prevalence.

At a time when Black men and women are more likely to be diagnosed with cancer at later stages when it is less treatable, [the Black & BRCA initiative] seeks to empower people to understand their family health history and take action to prevent cancer from one generation to the next, Domchek said.


1. Domchek SM, Yao S, Chen F, et al. Comparison of the prevalence of pathogenic variants in cancer susceptibility genes in black women and non-hispanic white women with breast cancer in the United States. Published online May 27, 2021.JAMA Oncol. doi:10.1001/jamaoncol.2021.1492

2. Black and white women have same mutations linked to breast cancer. News Release. Penn Medicine. June 11, 2021. Accessed June 16, 2021.

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Black and non-Hispanic White Women Found to Have No Differences in Genetic Risk for Breast Cancer - Cancer Network


What’s in your genes | The Crusader Newspaper Group – The Chicago Cusader

Thursday, June 24th, 2021

By Dr. DeLon Canterbury

Ever wonder why you may take a medication and have side effects, but a family member takes the same medication and does fine? Although your age, sex, weight, and health conditions could be factors

The answer may be in your genes!

Regardless of race, ethnicity, or gender, nearly 99.9 percent of EVERYONEs DNA is similar. For that 0.1 percent, there can be significant gene changes that impact how well or how poorly you tolerate a specific medication.

In other words, your DNA can affect whether you have a bad reaction to a drug, if a drug helps you, or has no effect.

Pharmacogenomics (Gene Testing/Precision Medicine) looks at how your DNA affects the way you respond to drugs. Its the study of specific gene changes that influence whether a medication could be lifesaving for one but potentially fatal for another.

The use and study of drug-gene testing has been around for 20 years. In the beginning, most insurance carriers did not cover it. Now, pharmacogenomics is widely available and affordable.

So why are you just hearing about Pharmacogenomics?

Sadly enough, health care still is not accessible to everyone, even those who have the best access still may not get the best answers!

As a concerned pharmacist with a passion for health equity and medication, GeriatRx can provide gene testing, identify potentially rare genetic disorders, as well as prevent you from taking ineffective and expensive medications.

It baffles me that the antibiotics, blood pressure, anxiety, and several other drugs we use daily were best assessed for a group of people that does not truly reflect the melting pot we proudly call USA.

Most modern, medicinal and pharmacological practices seen in our American health system stem from outdated, clinical studies with an overwhelming majority of white male subjects. Yes, we bleed the same, but how we respond to the drugs we take regularly, can be completely different!

GeriatRx has an absolute responsibility in sharing how using genetic tests can stop harmful and fatal medications from entering your body! GeriatRx works with your provider on how to best prescribe new drugs.

Want to know whats in your genes?

Get a personalized genetic test from an accessible and trusted pharmacist who can provide genetic testing anywhere in the country, GeriatRx.

Let GeriatRx advocate for you.

Dr. Canterbury, president/CEO of GeriatRx, Inc., is a Board-Certified Geriatric Pharmacist who focuses on the special needs of older patients that may have concurrent illnesses taking multiple medications. He is being trained as a Medicare and Medicaid specialist through the Seniors Health Insurance Information Program (SHIIP) and is a member of Durham, North Carolinas, African American COVID Task Force.

To learn more about GeriatRx and pharmacogenomics, contact Dr. Canterbury@cell: 404-484-5092; website:; email:

Looking to Advertise? Contact the Crusader for more information.

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What's in your genes | The Crusader Newspaper Group - The Chicago Cusader


Immusoft Announces Formation of Scientific Advisory Board – Business Wire

Thursday, June 24th, 2021

SEATTLE--(BUSINESS WIRE)--Immusoft, a cell therapy company dedicated to improving the lives of patients with rare diseases, announced today the formation of its Scientific Advisory Board (SAB) composed of world-renowned experts to provide external scientific review and high-level counsel on the Companys research and development programs.

The SAB will work closely with the Immusoft leadership team to advance and expand its leadership position in B cells as biofactories for therapeutic protein delivery, a novel approach that Immusoft has pioneered. The Company is currently preparing for the near-term clinical development of its lead investigational drug candidate ISP-001, a first-in-class investigational treatment for Hurler syndrome, the most severe form of mucopolysaccharidosis type 1 (MPS I), a rare lysosomal storage disease.

We are excited and privileged to have the opportunity to work with this group of rare disease and cell therapy experts, on the development of our pipeline, said Sean Ainsworth, Chief Executive Officer, Immusoft. These thought leaders bring tremendous understanding of rare diseases, as well as extensive experience in drug development from discovery through to late-stage clinical trials. We look forward to their continued contributions at Immusoft as we enter a new stage in advancing ISP-001 into clinical trials this year."

Members of the Immusoft Scientific Advisory Board are as follows:

Robert Sikorski, M.D., Ph.D., is Head of the SAB and consulting Chief Medical Officer at Immusoft. Dr. Sikorski currently serves as the Managing Director of Woodside Way Ventures, a consulting and investment firm that helps biotechnology companies and investors advance lifesaving technologies through clinical development. Prior to that, he was Chief Medical Officer of Five Prime Therapeutics (acquired by Amgen). Earlier in his career, he played a leading role in building MedImmunes oncology portfolio through partnering and acquisition efforts. Before joining Medimmune, he led late-stage clinical development and post-marketing efforts for several commercial drugs and drug candidates at Amgen. Dr. Sikorski began his career as a Howard Hughes Research Fellow and Visiting Scientist at the National Cancer Institute and the National Human Genome Research Institute in the laboratory of Nobel Laureate Harold Varmus. Additionally, he has served as an editor for the journal Science and Journal of the American Medical Association. Dr. Sikorski obtained his MD and PhD degrees as a Medical Scientist Training Program awardee at the Johns Hopkins School of Medicine.

Paula Cannon, Ph.D., is a Distinguished Professor of Molecular Microbiology and Immunology at the Keck School of Medicine of the University of Southern California, where she leads a research team that studies viruses, stem cells and gene therapy. She obtained her PhD from the University of Liverpool in the United Kingdom, and received postdoctoral training at both Oxford and Harvard universities. Her research uses gene editing technologies such as CRISPR/Cas9, to develop treatments for infectious and genetic diseases of the blood and immune systems. In 2010, her team was the first to show that gene editing could be used to mimic a natural mutation in the CCR5 gene that prevents HIV infection, and which has now progressed to a clinical trial in HIV-positive individuals.

Michael C. Carroll, Ph.D., is a Senior Investigator at Boston Children's Hospital and Professor of Pediatrics, Harvard Medical School. His recent research focuses on two major areas, i.e. neuroimmunology and peripheral autoimmunity. Using murine models of neuro-psychiatric lupus, his group is testing their hypothesis that interferon alpha from peripheral inflammation enters the brain and mediates synapse loss and symptoms of cognitive decline observed in patients. Following-up on a large genetic screen in schizophrenia patients, they recently reported that over-activation of a process known as complement-dependent, microglia-mediated synaptic pruning in novel strains of mice can induce psychiatric symptoms of schizophrenia. In a murine lupus model, his lab has identified that self-reactive B cells evolve with kinetics similar to that of foreign antigen responding B cells providing a novel explanation for epitope spreading. Dr. Carroll received his PhD from UT Southwestern Medical School and his postdoctoral training with the Nobel Laureate, Professor Rodney R. Porter at Oxford University. He is a recipient of awards from the Pew Foundation, American Arthritis Foundation and the National Alliance for Mental Health.

Hans-Peter Kiem, M.D., Ph.D. is the Stephanus Family Endowed Chair for Cell and Gene Therapy at Fred Hutchinson Cancer Research Center. He is a world-renowned pioneer in stem-cell and gene therapy and in the development of new gene-editing technologies. His focus has been the development of improved treatment and curative approaches for patients with genetic and infectious diseases or cancer. For gene editing, his lab works on the design and selection of enzymes, known as nucleases, which include CRISPR/Cas. These enzymes function as molecular scissors that are capable of accurately disabling defective genes. By combining gene therapys ability to repair problem-causing genes and stem cells regenerative capabilities, he hopes to achieve cures of diseases as diverse as HIV, leukemia and brain cancer. He is also pioneering in vivo gene therapy approaches to make gene therapy and gene editing more broadly available and accessible to patients and those living with HIV, especially in resource-limited settings. He received his M.D. and Ph.D. at the University of Ulm, Germany.

Bruce Levine, Ph.D., Barbara and Edward Netter Professor in Cancer Gene Therapy is the Founding Director of the Clinical Cell and Vaccine Production Facility in the Department of Pathology and Laboratory Medicine and the Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania. First-in-human adoptive immunotherapy trials include the first use of a lentiviral vector, the first infusions of gene edited cells, and the first use of lentivirally-modified cells to treat cancer. Dr. Levine has overseen the production, testing and release of 3,100 cellular products administered to more than 1,300 patients in clinical trials since 1996. Dr. Levine is a recipient of the William Osler Patient Oriented Research Award, the Wallace H. Coulter Award for Healthcare Innovation, the National Marrow Donor Program/Be The Match ONE Forum 2020 Dennis Confer Innovate Award, serves as President of the International Society for Cell and Gene Therapy, and on the Board of Directors of the Alliance for Regenerative Medicine. Dr. Levine received a B.A. in Biology from the University of Pennsylvania and a Ph.D. in Immunology and Infectious Diseases from Johns Hopkins University.

Peter Sage, Ph.D., is an Assistant Professor of Medicine at Harvard Medical School and an Associate Immunologist at Brigham and Womens Hospital. Dr. Sage is also a member of the Committee on Immunology (COI) at Harvard Medical School. Dr. Sage obtained his PhD in Immunology from Harvard Medical School in 2013, during which he received the Jeffrey Modell Prize. He completed a post-doctoral fellowship in the laboratory of Dr. Arlene Sharpe in the Department of Immunology at Harvard Medical School in 2017. Dr. Sage started his independent laboratory in 2017 at the Transplantation Research Center in the Division of Renal Medicine of Brigham and Womens Hospital. Dr. Sages laboratory focuses on studying how the immune system controls B cell and antibody responses in settings of health and disease.

About Immusoft

Immusoft is a cell therapy company focused on developing a novel therapies for rare diseases using a sustained delivery of protein therapeutics from a patients own cells. The company is developing a technology platform called Immune System Programming (ISP), which modifies a patients B cells and instructs the cells to produce gene-encoded medicines. The B cells that are reprogrammed using ISP become miniature drug factories that are expected to survive in patients for many years. The company is based in Seattle, WA. For more information, visit

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Immusoft Announces Formation of Scientific Advisory Board - Business Wire


Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress – Business…

Thursday, June 24th, 2021

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Pharmaceuticals Inc. (NASDAQ: ARWR) today presented positive interim results from AROHSD1001, an ongoing Phase 1/2 clinical study of ARO-HSD, the companys investigational RNA interference (RNAi) therapeutic being developed as a treatment for patients with alcohol-related and nonalcohol related liver diseases, such as nonalcoholic steatohepatitis (NASH), at The International Liver Congress - The Annual Meeting of the European Association for the Study of the Liver (EASL). The data demonstrate that ARO-HSD is the first investigational therapeutic to achieve robust reductions in messenger RNA (mRNA) and protein levels of hepatic HSD17B13, leading to reductions in alanine aminotransferase (ALT), a liver enzyme typically elevated in liver diseases including NASH.

Javier San Martin, M.D., chief medical officer at Arrowhead, said: Genetic studies have recently shown that HSD17B13 is a compelling target for multiple forms of liver disease. It is exciting to present clinical data at EASL demonstrating that ARO-HSD is the first investigational medicine using any therapeutic modality to achieve inhibition of HSD17B13 in patients. It is also highly encouraging to see ALT levels drop significantly following just two doses of ARO-HSD. These data and the strong genetic evidence of HSD17B13 as a potential therapeutic target provide us with increased confidence as we consider the design of potential late-stage clinical studies for ARO-HSD.

Pharmacodynamics and Efficacy

All five patients with suspected NASH showed a strong pharmacodynamic effect as measured by liver biopsy at Day 71. HSD17B13 mRNA was reduced by a mean of 84%, with a range of 62-96%. HSD17B13 protein was reduced by 83% or greater. Two patients had a protein decrease of 92% and 97%, while the other three patients Day 71 measurements were reduced to below the lower limit of quantitation.

Mean ALT reduction from baseline was 46%, with all patients showing reductions ranging from 26-53%. ARO-HSD is the first investigational RNAi therapeutic to demonstrate robust inhibition of hepatic HSD17B13 mRNA and protein expression with associated reductions in ALT.

Safety and Tolerability

ARO-HSD was well tolerated without any identified safety signals in healthy volunteers given a single dose of ARO-HSD at 25mg, 50mg, 100mg or 200 mg and in the 5 patients with suspected NASH given a single 100 mg dose of ARO-HSD on Days 1 and 29. Adverse events were similar between subjects receiving ARO-HSD or placebo. Two instances of mild injection site bruising and mild injection site erythema were observed in ARO-HSD treated subjects. There were no ARO-HSD associated grade 3 or 4 laboratory abnormalities (NCI-CTCAE v5.0), no drug related serious or severe adverse events, and there were no drug discontinuations.

AROHSD1001 (NCT04202354) is a Phase 1/2 single and multiple dose-escalating study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamic effects of ARO-HSD in up to 74 normal healthy volunteers and patients with NASH or suspected NASH. Additional exploratory objectives include the assessment of various measures of drug activity using liver biopsy.

Presentation Details

Title: ARO-HSD reduces hepatic HSD17B13 mRNA expression and protein levels in patients with suspected NASHAuthors: Edward Gane, et al.Type: Late-Breaking PosterDate and Time: June 23, 2021 at 8:00 CEST

A copy of the presentation materials may be accessed on the Events and Presentations page under the Investors section of the Arrowhead website. The abstract was also selected for inclusion in The International Liver Congress 2021 Official Scientific Press Conference: NAFLD/NASH on June 25, 2021.

HSD17B13 is a member of the hydroxysteroid dehydrogenase family involved in the metabolism of hormones, fatty acids, and bile acids. Published human genetic data indicate that a loss of function mutation in HSD17B13 provides strong protection against alcoholic hepatitis, cirrhosis, and NASH, with approximately 30-50% risk reduction compared to non-carriers.1

About Arrowhead Pharmaceuticals

Arrowhead Pharmaceuticals develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowheads RNAi-based therapeutics leverage this natural pathway of gene silencing.

For more information, please visit, or follow us on Twitter @ArrowheadPharma. To be added to the Company's email list and receive news directly, please visit

Safe Harbor Statement under the Private Securities Litigation Reform Act:

This news release contains forward-looking statements within the meaning of the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Any statements contained in this release except for historical information may be deemed to be forward-looking statements. Without limiting the generality of the foregoing, words such as may, will, expect, believe, anticipate, intend, plan, project, could, estimate, or continue are intended to identify such forward-looking statements. In addition, any statements that refer to projections of our future financial performance, trends in our business, expectations for our product pipeline, prospects or benefits of our collaborations with other companies, or other characterizations of future events or circumstances are forward-looking statements. These statements are based upon our current expectations and speak only as of the date hereof. Our actual results may differ materially and adversely from those expressed in any forward-looking statements as a result of numerous factors and uncertainties, including the impact of the ongoing COVID-19 pandemic on our business, the safety and efficacy of our product candidates, the duration and impact of regulatory delays in our clinical programs, our ability to finance our operations, the likelihood and timing of the receipt of future milestone and licensing fees, the future success of our scientific studies, our ability to successfully develop and commercialize drug candidates, the timing for starting and completing clinical trials, rapid technological change in our markets, the enforcement of our intellectual property rights, and the other risks and uncertainties described in our most recent Annual Report on Form 10-K, subsequent Quarterly Reports on Form 10-Q and other documents filed with the Securities and Exchange Commission from time to time. We assume no obligation to update or revise forward-looking statements to reflect new events or circumstances.

Source: Arrowhead Pharmaceuticals, Inc.


1 The New England Journal of Medicine. 2018, 1096-1106

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Arrowhead Presents Positive Interim Clinical Data on ARO-HSD Treatment in Patients with Suspected NASH at EASL International Liver Congress - Business...


Pacific Biosciences and Rady Children’s Institute for Genomic Medicine Announce its First Research Collaboration for Whole – GlobeNewswire

Thursday, June 24th, 2021

MENLO PARK, Calif., June 23, 2021 (GLOBE NEWSWIRE) -- Pacific Biosciences of California, Inc. (Nasdaq: PACB)(Pacific Biosciences or PacBio), a leading provider of high-quality, long-read sequencing platforms, and Rady Childrens Institute for Genomic Medicine (RCIGM), a mission-driven, non-profit seeking to save lives and improve outcomes for patients, clinicians and families, shared today that they are collaborating on a study which aims to identify potential disease-causing genetic variants and increase the solve rates of rare diseases.

The study is focused on long-read whole genome sequencing of rare disease cases for which previous short-read whole genome and exome sequencing yielded no answers. The study, which is currently underway, was able to detect variants that were not identified by short-read sequencing (SRS); of these, an average of 37 were missense mutations in known disease genes.

PacBio HiFi sequencing can identify numerous variants, both small and structural that are not readily detectable by SRS, said Matthew Bainbridge, Principal Investigator, and Associate Director of Clinical Genomics at RCIGM. We sequenced this cohort of patients to 10-30X depth of coverage using Pacific Biosciences HiFi long-read technology to assess whether there was an increase in the identification of these variants. We are very pleased by the preliminary results delivered in this collaboration with the team at PacBio.

It is estimated that as many as 25 million Americans approximately 1 in 13 people are affected by a rare, and often undiagnosed condition. In rare disease studies, conventional techniques for whole-genome and whole-exome analysis based on SRS typically led to identification of a causal variant in less than 50% of cases. Utilizing PacBios Single Molecule, Real-Time (SMRT) Sequencing technologyto generate highly accurate long-reads, known asHiFi reads,clinical researchers have demonstrated that they can detect disease-causing structural and small variants missed by short-read sequencing platforms. This study is designed to evaluate the rate at which HiFi sequencing identifies overlooked causal variation.

It is an honor to collaborate with the innovative pediatric translational researchers at RCIGM to bring HiFi Sequencing data to bear on some of their most difficult cases of rare pediatric disease, and hopefully give individuals and families answers regarding potential underlying genetic variants, which may ultimately provide healthcare providers with insights to end their diagnostic odysseys, said Christian Henry, CEO and President at PacBio.

Weve been aware that theres a subset of seriously ill babies and children who dont receive a diagnosis with current sequencing methods, but based on their symptoms, were fairly certain that they have an underpinning genetic disease, said Stephen Kingsmore, MD, DSc, President and CEO of Radys Childrens Institute for Genomic Medicine. With this new technology, we are excited to see how many more of these children and families will receive additional insight regarding the identification of potential disease-causing genetic variants.

About Pacific BiosciencesPacific Biosciences of California, Inc. (NASDAQ: PACB) is empowering life scientists with highly accurate long-read sequencing. The companys innovative instruments are based on Single Molecule, Real-Time (SMRT) Sequencing technology, which delivers a comprehensive view of genomes, transcriptomes, and epigenomes, enabling access to the full spectrum of genetic variation in any organism. Cited in thousands of peer-reviewed publications, PacBio sequencing systems are in use by scientists around the world to drive discovery in human biomedical research, plant and animal sciences, and microbiology. For more information, please visitwww.pacb.comand follow@PacBio.

About Rady Childrens Institute for Genomic MedicineWe are transforming pediatric critical care by advancing disease-specific healthcare for infants and children with rare disease. Discoveries at the Institute are enabling rapid diagnosis and targeted treatment of critically ill newborns and pediatric patients at Rady Childrens Hospital-San Diego and a growing network of more than 60 childrens hospitals nationwide. The vision is to expand delivery of this life-changing technology to enable the practice of Rapid Precision Medicine at childrens hospitals across the nation and the world. RCIGM is a non-profit, research institute of Rady Childrens Hospital and Health Center. Learn more at Follow us on Twitter and LinkedIn.

PacBio products are provided for Research Use Only. Not for use in diagnostic procedures.

Forward-Looking Statements This press release may contain forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and the U.S. Private Securities Litigation Reform Act of 1995, including statements relating to the collaboration between PacBio and RCIGM, potential use of SMRT sequencing technology to identify, and increase the rate of identification of, potential disease-causing genetic variants in rare disease, the potential of HiFi data, the applications, insights, and attributes of SMRT sequencing technology, and the benefits of PacBio sequencing. Readers are cautioned not to place undue reliance on these forward-looking statements and any such forward-looking statements are qualified in their entirety by reference to the following cautionary statements. All forward-looking statements speak only as of the date of this press release and are based on current expectations and involve a number of assumptions, risks and uncertainties that could cause the actual results to differ materially from such forward-looking statements. Readers are strongly encouraged to read the full cautionary statements contained in the Companys filings with the Securities and Exchange Commission, including the risks set forth in the companys Forms 8-K, 10-K, and 10-Q. The Company disclaims any obligation to update or revise any forward-looking statements.


Investors:Todd Friedman+1 (650)

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Pacific Biosciences and Rady Children's Institute for Genomic Medicine Announce its First Research Collaboration for Whole - GlobeNewswire


Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers – Yale School of Medicine

Thursday, June 24th, 2021

Despite the challenges of COVID-19, Yale Pulmonary, Critical Care & Sleep Medicine (Yale-PCCSM) section members at Yale School of Medicine (YSM) continued their work on scientific papers. Here is a list of their recent original research papers in which either the first or last author is a Yale-PCCSM section member. Hannah Oakland and Jacqueline Geer are fellows.

Nucleotide-binding domain and leucine-rich-repeat-containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung-like changes. Shin HJ, Kim SH, Park HJ, Shin MS, Kang I, Kang MJ. Aging Cell. 2021 Jun 4; 2021 Jun 4. PMID: 34087956.

Transcriptomics of bronchoalveolar lavage cells identifies new molecular endotypes of sarcoidosis. Vukmirovic M, Yan X, Gibson KF, Gulati M, Schupp JC, DeIuliis G, Adams TS, Hu B, Mihaljinec A, Woolard TN, Lynn H, Emeagwali N, Herzog EL, Chen ES, Morris A, Leader JK, Zhang Y, Garcia JGN, Maier LA, Collman RG, Drake WP, Becich MJ, Hochheiser H, Wisniewski SR, Benos PV, Moller DR, Prasse A, Koth LL, Kaminski N. Eur Respir J. 2021 Jun 3; 2021 Jun 3. PMID: 34083402.

Functional Effects of Intervening Illnesses and Injuries After Critical Illness in Older Persons. Gill TM, Han L, Gahbauer EA, Leo-Summers L, Murphy TE, Ferrante LE. Crit Care Med. 2021 Jun 1. PMID: 33497167.

The Arterial Load and Right Ventricular-Vascular Coupling in Pulmonary Hypertension. Oakland HT, Joseph P, Naeije R, Elassal A, Cullinan M, Heerdt PM, Singh I. J Appl Physiol (1985). 2021 May 27; 2021 May 27. PMID: 34043473.

Integrated Single Cell Atlas of Endothelial Cells of the Human Lung. Schupp JC, Adams TS, Cosme C Jr, Raredon MSB, Yuan Y, Omote N, Poli S, Chioccioli M, Rose KA, Manning EP, Sauler M, DeIuliis G, Ahangari F, Neumark N, Habermann AC, Gutierrez AJ, Bui LT, Lafyatis R, Pierce RW, Meyer KB, Nawijn MC, Teichmann SA, Banovich NE, Kropski JA, Niklason LE, Pe'er D, Yan X, Homer RJ, Rosas IO, Kaminski N. Circulation. 2021 May 25; 2021 May 25. PMID: 34030460.

G2S3: A gene graph-based imputation method for single-cell RNA sequencing data. Wu W, Liu Y, Dai Q, Yan X, Wang Z. PLoS Comput Biol. 2021 May 18; 2021 May 18. PMID: 34003861.

Surveillance of adverse drug events associated with tocilizumab in hospitalized veterans with coronavirus disease 2019 (COVID-19) to inform patient safety and pandemic preparedness. Datta R, Barrett A, Burk M, Salone C, Au A, Cunningham F, Fisher A, Dembry LM, Akgn KM. Infect Control Hosp Epidemiol. 2021 May 14; 2021 May 14. PMID: 33985598.

SPLUNC1: a novel marker of cystic fibrosis exacerbations. Khanal S, Webster M, Niu N, Zielonka J, Nunez M, Chupp G, Slade MD, Cohn L, Sauler M, Gomez JL, Tarran R, Sharma L, Dela Cruz CS, Egan M, Laguna T, Britto CJ. Eur Respir J. 2021 May 6; 2021 May 6. PMID: 33958427.

PINK1 Inhibits Multimeric Aggregation and Signaling of MAVS and MAVS-Dependent Lung Pathology. Kim SH, Shin HJ, Yoon CM, Lee SW, Sharma L, Dela Cruz CS, Kang MJ. Am J Respir Cell Mol Biol. 2021 May. PMID: 33577398.

Obstructive Sleep Apnea as a Risk Factor for Intracerebral Hemorrhage. Geer JH, Falcone GJ, Vanent KN, Leasure AC, Woo D, Molano JR, Sansing LH, Langefeld CD, Pisani MA, Yaggi HK, Sheth KN. Stroke. 2021 May; 2021 Apr 8. PMID: 33827242.

Single-cell characterization of a model of poly I:C-stimulated peripheral blood mononuclear cells in severe asthma. Chen A, Diaz-Soto MP, Sanmamed MF, Adams T, Schupp JC, Gupta A, Britto C, Sauler M, Yan X, Liu Q, Nino G, Cruz CSD, Chupp GL, Gomez JL. Respir Res. 2021 Apr 26; 2021 Apr 26. PMID: 33902571.

Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis. Kim SH, Lee JY, Yoon CM, Shin HJ, Lee SW, Rosas I, Herzog E, Dela Cruz CS, Kaminski N, Kang MJ. Eur Respir J. 2021 Apr; 2021 Apr 15. PMID: 33093124.

Elevated IL-15 concentrations in the sarcoidosis lung is independent of granuloma burden and disease phenotypes. Minasyan M, Sharma L, Pivarnik T, Liu W, Adams T, Bermejo S, Peng X, Liu A, Ishikawa G, Perry C, Kaminski N, Gulati M, Herzog EL, Dela Cruz CS, Ryu C. Am J Physiol Lung Cell Mol Physiol. 2021 Apr 14; 2021 Apr 14. PMID: 33851886.

Randomized trial of physical activity on quality of life and lung cancer biomarkers in patients with advanced stage lung cancer: a pilot study. Bade BC, Gan G, Li F, Lu L, Tanoue L, Silvestri GA, Irwin ML. BMC Cancer. 2021 Apr 1; 2021 Apr 1. PMID: 33794808.

Added Diagnostic Utility of Clinical Metagenomics for the Diagnosis of Pneumonia in Immunocompromised Adults. Azar MM, Schlaberg R, Malinis MF, Bermejo S, Schwarz T, Xie H, Dela Cruz CS. Chest. 2021 Apr; 2020 Nov 18. PMID: 33217418.

The Association Between Hospital End-of-Life Care Quality and the Care Received Among Patients With Heart Failure. Feder SL, Tate J, Ersek M, Krishnan S, Chaudhry SI, Bastian LA, Rolnick J, Kutney-Lee A, Akgn KM. J Pain Symptom Manage. 2021 Apr; 2020 Sep 12. PMID: 32931904.


Genetic Variants of SARS-CoV-2: What do we know so far? Jamil S, Shafazand S, Pasnick S, Carlos WG, Maves R, Dela Cruz C. Am J Respir Crit Care Med. 2021 May 10; 2021 May 10. PMID: 33970826.

Sleep during lockdown. Kryger MH. Sleep Health. 2021 May 8; 2021 May 8. PMID: 33975818.

Showing a dream. Kryger MH. Sleep Health. 2021 Apr; 2021 Mar 5. PMID: 33685831

2020 Updated Asthma Guidelines: Bronchial thermoplasty in the management of asthma. Castro M, Chupp G. J Allergy Clin Immunol. 2021 May; 2021 Mar 2. PMID: 33667476.

The Section of Pulmonary, Critical Care and Sleep Medicine is one of the eleven sections within YSMs Department of Internal Medicine. To learn more about Yale-PCCSM, visit PCCSMs website, or follow them on Facebook and Twitter.

Despite the challenges of COVID-19, Yale-PCCSM section members continued their work on scientific papers - Yale School of Medicine


Veritas Intercontinental: Genetics makes it possible to identify cardiovascular genetic risk and prevent cardiac accidents such as those that have…

Thursday, June 24th, 2021

MADRID, June 22, 2021 /PRNewswire/ -- We have recently witnessed, once again, a professional athlete suffering a cardiovascular attack during a match. This type of incidence and the possible fatal consequences result from an individual's genetic makeup. Genetic science now makes it possible to know whether a person has an elevated risk to suffer this type of cardiovascular accident and to avoid one of the main causes of death in the world, with more than 17 million deaths each year.

The role of genetics as a diagnostic element has been fundamental for several years, as Dr. Izquierdo, Chief Medical Officer of Veritas Intercontinental, says: "Sudden cardiac death (SCD) is mainly due to coronary pathologies, especially in patients over 40 years old, but in younger patients, such as many high-performance professional athletes, the contribution of genetic factors to the pathogenesis of SCD is a key factor, since we usually find a clear pattern of family inheritance at its origin, such as cardiomyopathies or channelopathies".

To help in the detection and prevention of Cardio Vascular Disease (CVD), Veritas Intercontinental offers the myCardiogenetic service, an innovative Exome sequencing and interpretation service, focused on genes related to hereditary heart diseases.

The analysis includes all genes recommended by the American Heart Association (AHA) analyzing 100 genes based on their relationship with different hereditary heart diseases. The service includes genetic counseling for the prescribing specialist, which is essential for the correct interpretation of the results and clinical management of the patient.

"myCardio,"explains Dr. Luis Izquierdo, "makes it possible to tackle the main types of cardiac disorders of hereditary origin and offers enormously valuable information to avoid the disease or to treat it much more efficiently. Until now, genetic tests related to hereditary heart disease have been very focused on certain pathologies, when it has been shown that there are many interactions between different heart conditions. myCardio allows a comprehensive approach to heart disease, with a new perspective that has been shown to be much more effective".


Whole exome sequencing (WES) is the most appropriate tool to address the genetic heterogeneity present in inherited cardiovascular disease. Recent studies show a very significant improvement in diagnostic performance using exome sequencing compared to panels, since a high number of cases in which several mutations are recorded simultaneously are observed. The advantages of the exome are more prominent in those cases in which there is no high clinical suspicion, as well as those in which the patient has been recovered after an episode of sudden death.

The service covers the study of hereditary predisposition to Primary Cardiomyopathies, Metabolic Cardiomyopathies, Channelopathies and Arrhythmias, Syndromes with Vascular Affection, Rasopathies,other syndromes linked to cardiac pathology and other risk factors (Ischemic Heart Disease) such as Familial Hypercholesterolemia.

About Veritas Intercontinental

Veritas Intercontinental was founded in 2018 by Dr. Luis Izquierdo, Dr. Vincenzo Cirigliano and Javier de Echevarra, who have accumulated extensive experience in the field of genetics, diagnostics, and biotechnology, initially linked to Veritas Genetics, a company founded in 2014 by Prof. George Church, one of the pioneers in preventive medicine. Veritas was born with the aim of making genome sequencing and its clinical interpretation available to all citizens as a tool to prevent diseases and improve health and quality of life.

Since its inception, Veritas Intercontinental has led the activity and development of the Veritas market in Europe, Latin America, the Middle East, and Japan; with the aim of making genomics an everyday tool used for proactive healthcare management.

Based on its leadership in the application of preventive genomic medicine (myGenome), Veritas Intercontinental has expanded its offer to other areas such as perinatal medicine (myPrenatal -NIPT- and myNewborn -neonatal screening-), oncology (myCancerRisk), or the mentioned cardiovascular pathologies (myCardio), thus becoming the benchmark in advanced genomics services.

For further information

Marta Pereiro[emailprotected]+34 915 623 675

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs – Newswise

Thursday, June 24th, 2021

Newswise A new study by Dana-Farber Cancer Institute researchers has given scientists their first look at the genomic landscape of tumors that have grown resistant to drugs targeting the abnormal KRASG12C protein. Their work shows that, far from adopting a common route to becoming resistant, the cells take a strikingly diverse set of avenues, often several at a time.

The findings, reported online today in the New England Journal of Medicine, underscore the need for new drugs that inhibit KRAS differently than current agents do. And, because resistance can arise through many different mechanisms, effective treatment for these cancers will likely require combinations of KRAS inhibitors and other targeted drugs.

Mutations in the KRAS gene are fairly common across cancer types, said Dana-Farbers Mark Awad, MD, PhD, the co-first author of the paper with Shengwu Liu, PhD, also of Dana-Farber. The particular mutation we focused on in this study, KRASG12C, is found in about 13% of non-small cell lung cancers [NSCLC], where its often associated with tobacco use, in up to 3% of colorectal cancers, and less frequently in a range of other cancers. While no targeted therapy has been approved for this specific molecular subtype, two inhibitors of the KRASG12C protein adagrasib and sotorasib have shown promise in clinical trials, especially in patients with NSCLC.

While results from these early clinical trials are encouraging, the cancer usually becomes resistant to these drugs, Awad continued. The mechanisms of resistance the genomic and other changes that occur that allow the cancer to begin growing again are largely unknown. This study sought to identify them.

In a multi-institutional effort, researchers collected tumor samples from 38 patients with cancers carrying KRASG12C mutations 27 with NSCLC, 10 with colorectal cancer, and one with cancer of the appendix. Analysis of the samples uncovered possible causes of resistance to adagrasib in 17 of the patients, seven of whom had multiple causes.

The resistance mechanisms fell into three categories:

The number of patients with KRAS alterations and non-KRAS genetic abnormalities was roughly equal, and many patients had both types of resistance mechanisms.

The effort to uncover KRAS mutations associated with drug resistance was also led by the studys senior author, Andrew Aguirre, MD, PhD, of Dana-Farber, Brigham and Womens Hospital, and the Broad Institute of MIT and Harvard. Aguirre and his colleagues created a series of cell lines, each containing the G12C mutation plus an additional mutation elsewhere in the KRAS gene. The set represented every possible second mutation in KRASG12C that would give rise to an abnormal protein. The researchers then ran tests to see which of the doubly mutated genes gave cells the ability to become resistant to sotorasib or an adagrasib-like compound. They also tested the further-mutated versions of KRASG12C that the team had identified in patients.

They found that some of the new mutations conferred resistance to both agents, whereas others provided resistance to just one.

In addition to identifying resistance mutations that have already occurred in patients receiving adagrasib, our study also provides an atlas of all possible mutations in KRASG12C that can cause resistance to adagrasib and/or sotorasib, Aguirre said. These results will be a valuable resource for oncologists to interpret future acquired mutations that occur in patients who become resistant to these drugs and may be used to guide the choice of which KRASG12C inhibitor is right for each patient.

The study results point to the variety of ways cancers with KRASG12C mutations can overcome the effects of adagrasib, the authors say. Cancers with the KRASG12C mutation constitute a large proportion of all lung cancers, and many pharmaceutical companies are developing KRASG12C inhibitors, Awad observed. The hope is that studies such as this, which uncover resistance mechanisms, will help drive future studies of combination therapies to delay or prevent resistance or overcome it when it occurs.

The study co-authors are Julien Dilly, MS, Joseph O. Jacobson, MD, MSc, Kristen E. Lowder, Hanrong Feng, MA, Brian M. Wolpin, MD, MPH, and Pasi A. Jnne, MD, PhD, of Dana-Farber; Kevin M. Haigis, PhD, of Dana-Farber and the Broad Institute; Igor I. Rybkin, MD, PhD, of Henry Ford Cancer Institute; Kathryn C. Arbour, MD, Gregory J. Riely, MD, PhD, and Piro Lito, MD, PhD, of Memorial Sloan Kettering Cancer Institute; Viola W. Zhu, MD, PhD, Shannon S. Zhang, MD, and Sai-Hong Ignatius Ou, MD, PhD, of the University of California Irvine; Melissa L. Johnson, MD, of Sarah Cannon Research Institute; Rebecca S. Heist, MD, MPH, and Yin P. Hung, MD, PhD, of Massachusetts General Hospital; Tejas Patil, MD, of the University of Colorado; Xiaoping Yang, PhD, Nicole S. Persky, PhD, and David E. Root, PhD, of the Broad Institute; Lynette M. Sholl, MD, of BWH; Julie Wiese, and Jason Christiansen, PhD, of Boundless Bio, La Jolla, Calif.; Jessica Lee, MS, and Alexa B. Schrock, PhD, of Foundation Medicine, Cambridge, Mass.; Lee P. Lim, PhD, Kavita Garg, PhD, and Mark Li, of Resolution Bioscience, Kirkland, Wash.; and Lars D. Engstrom, Laura Waters, MS, J. David Lawson, PhD, Peter Olson, PhD, and James G. Christensen, PhD, of Mirati Therapeutics, San Diego, Calif.

The research was funded by Mirati Therapeutics; the Lustgarten Foundation; the Dana-Farber Cancer Institute Hale Center for Pancreatic Cancer Research; the National Cancer Institute (grants KO8CA218420-02, P50CA127003, U01CA20171, 1R01CA230745-01, and 1R01CA230267-01A1); Stand Up to Cancer; the Pancreatic Cancer Action Network; the Noble Effort Fund; the Wexler Family Fund; Promises for Purple; the Bob Parsons Fund; the Pew Charitable Trusts; the Damon Runyon Cancer Research Foundation; the Josie Robertson Investigator Program at Memorial Sloan Kettering; the Mark Foundation for Cancer Research; and the American Cancer Society.

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New Research Uncovers How Cancers with Common Gene Mutation Develop Resistance to Targeted Drugs - Newswise


Celebrate the Third Annual Medical Genetics Awareness Week April 13-16, 2021 – PRNewswire

Sunday, February 14th, 2021

BETHESDA, Md., Feb. 11, 2021 /PRNewswire/ --The third annual Medical Genetics Awareness Week will be celebrated April 1316, 2021. Through Medical Genetics Awareness Week, the American College of Medical Genetics and Genomics (ACMG) aims to promote awareness of the importance of medical genetics professionals on the healthcare team, including medical geneticists, laboratory geneticists, genetic counselors, nurses and physician assistants. The theme of Medical Genetics Awareness Week is "Celebrating the Contributions of the Entire Medical Genetics Team to Patient Care and Public Health."

New for 2021 are high-quality face masks and a Zoom virtual background to help individuals "Share Your Medical Genetics Pride." Participants can share their pictures to social media wearing a Medical Genetics Awareness Week face mask (free for ACMG members) or a Medical Genetics Awareness Week hashtag button; using a new Medical Genetics Awareness Week Zoom virtual background; or displaying a Medical Genetics Awareness Week sticker.

Since 2019, Medical Genetics Awareness Week has brought together people from across the globe to celebrate the important work of medical genetics professionals. Medical Genetics Awareness Week is celebrated to recognize the critical contributions that medical genetics healthcare professionals make in the diagnosis, management and prevention of genetic diseases, and the difference these professionals make in the lives of patients and families. Medical Genetics Awareness Week is also intended to educate other healthcare professionals and students and trainees on who medical geneticists are, how they are trained and what they do in the clinic and laboratory.

Also new for 2021 are themed days that will include a Diversity Day and a Student and Trainee Day. Follow Medical Genetics Awareness Week on social media by searching the #MedicalGeneticsAwareness hashtagand sign up to receive news and updates about Medical Genetics Awareness Week by clicking here. Log in (or create a free ACMG account) and, on the privacy preferences page, opt in to receive news and updates about Medical Genetics Awareness Week.

"Medical genetics and genomics is now deeply wedged into nearly all disciplines of medicine," said ACMG President Anthony R. Gregg, MD, MBA, FACOG, FACMG. "It is a natural extension that we remind the public and all healthcare professionals that those of us who practice medical genetics in clinics, clinical laboratories and research environments work tirelessly and with great enthusiasm. Our singular common goal is to bring accurate genetic information to the bedside that will improve people's lives."

Events related to Medical Genetics Awareness Week will be held during the ACMG Annual Clinical Genetics Meeting A Virtual Experience, April 1316, 2021, but participants don't need to be a meeting registrant to participate in the week's activities. The ACMG Annual Meeting is the largest conference specifically for clinical and laboratory geneticists in the United States. Those interested in collaborating with ACMG to celebrate Medical Genetics Awareness Week, holding their own events or becoming an "ambassador" for medical genetics are invited to email ACMG Communications Coordinator Reymar Santos at [emailprotected]for more information.

"Medical genetics is for all of us," said Max Muenke, MD, FACMG, ACMG'schief executive officer. "I am delighted to celebrate my colleagues in this important field: genetic counselors, laboratory geneticists, medical geneticists, and other allied healthcare professionals who are committed to optimal patient care."

Visit the Medical Genetics Awareness Week web pageson ACMG's website for resources and tips designed to support the week's celebrationsand to join the Medical Genetics Awareness Week email list. When posting on social media, participants are encouraged to tag @TheACMG and include the following hashtags in posts related to Medical Genetics Awareness Week:


About the American College of Medical Genetics and Genomics (ACMG) and ACMG Foundation

Founded in 1991, the American College of Medical Genetics and Genomics (ACMG) is the only nationally recognized medical society dedicated to improving health through the clinical practice of medical genetics and genomics and the only medical specialty society in the US that represents the full spectrum of medical genetics disciplines in a single organization. The ACMG is the largest membership organization specifically for medical geneticists, providing education, resources and a voice for more than 2,400 clinical and laboratory geneticists, genetic counselors and other healthcare professionals, nearly 80% of whom are board certified in the medical genetics specialties. ACMG's mission is to improve health through the clinical and laboratory practice of medical genetics as well as through advocacy, education and clinical research, and to guide the safe and effective integration of genetics and genomics into all of medicine and healthcare, resulting in improved personal and public health. Four overarching strategies guide ACMG's work: 1) to reinforce and expand ACMG's position as the leader and prominent authority in the field of medical genetics and genomics, including clinical research, while educating the medical community on the significant role that genetics and genomics will continue to play in understanding, preventing, treating and curing disease; 2) to secure and expand the professional workforce for medical genetics and genomics; 3) to advocate for the specialty; and 4) to provide best-in-class education to members and nonmembers. Genetics in Medicine, published monthly, is the official ACMG journal. ACMG's website ( offers resources including policy statements, practice guidelines, educational programs and a 'Find a Genetic Service' tool. The educational and public health programs of the ACMG are dependent upon charitable gifts from corporations, foundations and individuals through the ACMG Foundation for Genetic and Genomic Medicine.

Kathy Moran, MBA[emailprotected]

SOURCE American College of Medical Genetics and Genomics

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Celebrate the Third Annual Medical Genetics Awareness Week April 13-16, 2021 - PRNewswire


How will WNY fare in the race between vaccines and coronavirus variants? – Buffalo News

Sunday, February 14th, 2021

Doctors and researchers understand much more now than they did a year ago about virus spread and the damage it can inflict. Treatments have improved greatly. It is apparent who is most at risk, although people of all ages, races and socio-economic backgrounds have been hospitalized and died.

Public health leaders and infectious disease specialists includingDr. John Sellick Jr., aprofessor of medicine at the University at Buffalo Jacobs School of Medicine and Biomedical Sciences, encourage Western New Yorkers to practice Covid-prevention measures and refrain from travel until vaccination rates lower fears about the spread of new coronavirus variants.

The vaccination race will be critical to whether we need to resume the kinds of lockdowns that have taken place in recent months in Great Britain, Sellick said, but again, its back to the basics: masks, use of physical distancing, avoiding crowds, good hand hygiene. The more we do that, the more we're going to neutralize the effect of one of these more easily transmissible strains.

Q: What if a relative or a friend is planning a trip south or west to enjoy warmer weather?

I don't want those people around me for even five minutes, Sellick said, because travel in such uncertain times especially to places with beaches, outdoor restaurants and other magnets for large gatherings raises the risk of contracting the virus, or a variant, and endangering others.

Q: What states pose the greatest risk for contracting and spreading the virus?

The positive virus test rate in the region at the end of last week was about 3.5%. The rate in Florida was twice that, and it was more than three times higher in Texas and Georgia. The rate was at least five times higher in Iowa, Idaho, Kansas, Kentucky and South Dakota, according toBeckers Hospital Review.

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How will WNY fare in the race between vaccines and coronavirus variants? - Buffalo News


Myriad Genetics to Participate in Multiple Upcoming Health and Technology Conferences – GlobeNewswire

Sunday, February 14th, 2021

SALT LAKE CITY, Feb. 11, 2021 (GLOBE NEWSWIRE) -- Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in genetic testing and precision medicine, announced today that it will participate at multiple upcoming health and technology conferences, sharing insights on how the company is intensifying its focus on serving patients and healthcare providers in Womens Health, Oncology and Mental Health.

Paul J. Diaz, president and CEO at Myriad Genetics, and R. Bryan Riggsbee, CFO, will participate in a fireside chat at the BTIG Virtual MedTech, Digital Health, Life Science & Diagnostic Tools Conference on February 19 at 10:30 a.m. EST.

On February 24, 2021, Mr. Riggsbee will participate in a fireside chat at the Leerink Global Healthcare Conference at 5:00 p.m. EST.

On March 2, 2021, Mr. Diaz will participate in a fireside chat at the Cowen Annual Healthcare Conference at 9:50 a.m. EST.

The presentations will be available through a live audio webcast link in the investor information section of Myriads website at

About Myriad GeneticsMyriad Genetics, Inc. is a leading genetic testing and precision medicine company dedicated to improving health and transforming patient lives worldwide. Myriad discovers and commercializes genetic tests that: determine the risk of developing disease, accurately diagnose disease, assess the risk of disease progression, and guide treatment decisions across medical specialties where critical genetic insights can significantly improve patient care and lower healthcare costs. For more information, visit the Company's website:

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, Vectra, Prequel, Foresight, GeneSight, riskScore and Prolaris 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.

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Myriad Genetics to Participate in Multiple Upcoming Health and Technology Conferences - GlobeNewswire


ASCO GU 2021: The Landscape of Genetic Alterations Using ctDNA-based Comprehensive Genomic Profiling in Pat… – UroToday

Sunday, February 14th, 2021

(, both of the tumor (somatic) and germline, are increasingly being incorporated into clinical oncologic care, both with regard to specific targeted therapy selections (e.g.PARP inhibitors) and therapy intensity (e.g.aggressive variants,e.g.genomic alterations inRB1, TP53).Often re-biopsy can impose an additional barrier for a patient, or is limited by site of metastasis, such as bone.These realities are justifications for the herald of the non-invasive evaluation of tumor genomics from the circulating (blood) compartment via circulating tumor DNA (ctDNA).Herein, Dr. Tukachinsky and colleagues endeavored to evaluate via hybrid-capture-based targeted gene panel next generation sequencing (NGS) the landscape of genomic alterations (GA) found in the plasma of patients with metastatic castration-resistant prostate cancer (mCRPC), and, in a subset, evaluate concordance with tissue-based NGS assessments.

Plasma samples were culled from 3334 men with advanced prostate cancer, including 1674 subjects from the TRITON2/3 studies of rucaparib and 1660 non-trial clinical samples.The observed GA landscape was compared to 2006 metastatic biopsies, with concordance assessed in 837 patients.In keeping with previous reports of ctDNA burden, 94% (3127) of subjects had detectable ctDNA with 8.8% (295) with mutations inBRCA1/2.Concordance with tissue evidence ofBRCA1/2mutations was observed in 93% of evaluable subjects (67/72) and 20 subjects had evidence of such mutationsonlyin ctDNA.Notably, subclonal reversion mutations inBRCA1/2were observed in 10 of 1660 routine clinical specimens, suggesting a mechanism for PARPi resistance, at least in a subpopulation evaluated.

Alterations inAR, the gene encoding the androgen receptor, were detected in 42% (940/2213) samples, including amplifications and hotspot mutations.Among the mutations detected are specific alterations which confer resistance to commonly used highly-potent ARSIs, such as abiraterone acetate and enzalutamide.The authors also describe a subset of samples with rare compound double mutations and novel potentially activating mutations in AR. Additional GAs were detected in relevant signaling pathways including PI3K/AKT/mTOR (14%), WNT/beta-catenin (17%), and RAS/RAF (5%).Microsatellite instability was rare (1.4% of 2213 patients).

These data lend further support to the relative reliability (as compared to tissue assays) of using plasma for evaluating relevant tumor genomic alterations in the advanced metastatic setting, reflecting genomics data demonstrating that dominant metastatic clones found at autopsy can be found in the circulating compartment1.This is particularly powerful as detection of resistant subclones that may not be in a tissue-based sample, either because these cells reflect occult or unsampled metastatic samples, could impact therapeutic decisions. It should be considered that use of subjects from the TRITON studies, which comprised approximately half of the cohort may result in higher rates of observed GAs inBRCA1/2than in daily practice, given the enrichment in such genomic alterations as ground truth in this group.As noted by the authors, the limitations of the assay in these studies includes an inability to detect deletions inBRCA1/BRCA2, as well as other clinically-relevant commonly-deleted prostate cancer genes (e.g. PTEN). Further evaluation using orthogonal assays, such as RNAseq, would add additional detail, particularly along the AR signaling axis, to these promising results. Finally, the authors astutely recommend that a degree of caution must be taken when interpreting liquid biopsy results, given the influence of alterations representing clonal hematopoiesis.

Publication of full length publication can be found in the February 8thissue ofClinical Cancer Research.

Presented by: Hanna Tukachinsky, PhD, Foundation Medicine Inc., Cambridge, MA

Written by: Jones Nauseef MD, PhD. Fellow, Division of Hematology and Oncology, Weill Cornell Medicine/New York Presbyterian Hospital. Twitter: @DrJonesNauseefduring the2021 ASCO Genitourinary Cancers Symposium (ASCO GU), February 11th to 13th, 2021

References:1. Woodcock DJ, Riabchenko E, Taavitsainen S, et al., Prostate cancer evolution from multilineage primary to single lineage metastases with implications for liquid biopsy. Nature Comm. 11:5070 (2020). DOI:10.1038/s41467-020-18843-5.

ASCO GU 2021: The Landscape of Genetic Alterations Using ctDNA-based Comprehensive Genomic Profiling in Pat... - UroToday


The Human Genome and the Making of a Skeptical Biologist – Scientific American

Sunday, February 14th, 2021

Graduate and medical school interviews are not democratic spaces. Whatever the interviewer says during that 30 minutes, is the rule of law.

Surely there were policies about the legality of certain questions, but those often arent operational during the interview. Those of us in the chair only hope that the questions arent too difficult, that the interviewer doesnt focus on (or conjure) a flaw in our application, spend the 30 minutes of our engagement berating us for it, breaking our self-esteem for all of eternity.

One interview day during the fall of 2001, however, was special. Interviewer Z, as we will call them, had a different agenda than most.

Across a wooden desk they sat, their attention focused on a computer slightly off to my left. They tilted the monitor so that we could both see it, and walked me through a few of the things that they had worked on.

Interviewer Z was a physician turned basic scientist who made a name for themself as a virologist. In the last several years, they had moved into studying adenovirus-associated vectors (AAV) that were being used as delivery vehicles for gene therapy.

They told me that I was a promising researcher and were curious why I wanted to bother with clinical medicine at all (they were onto something). In light of that, they preferred to spend our interview time teaching me how to build a successful scientific career.

Their tips to building a career? Identify somethinga gene, a protein, a pathway, perhaps an organismand study a feature of it that no one has, in great depth. Study it well enough to publish results in a reasonably well-regarded journal. Present broadly on this topic. Talk to multiple audiences, make a case for why the thing you work on reveals everything about everything.

The advice they were giving me was about how they were able to be nimble, relevant and well-funded. I sat and listened closely.

With your microbiology background, you need to find a way to cash in on the human genome craze. Us virologists are going to win a Nobel Prize for it, you know.

They learned over and said, almost under their breath:

This is how we win.


Before this interview, I had never thought about scientific ambition in such organized terms. My scientific mentors until that pointa young physical chemist named Vernon Morris, and bacterial geneticist Susan Gottesmandidnt appear to work that way. That is, while each had their strategies (like all successful scientists do), they didnt describe their scientific ambitions like a military operation: no fields to take over, no one to defeat, nothing to win.

From my vantage point (nave at the time), they seemed to love the ideas, loved working with people, and only wanted to do good in the world (their behaviors reflected that).

My experience with Interviewer Z took place less than a year after the announcement of the completion of the first draft of the human genome. The announcement shook the world but was especially exciting for me because it was something of a local affair. I was working at the National Cancer Institute (NCI) at the time, on the campus of the National Institutes of Health (NIH) in Bethesda, Md. (where the Human Genome Project lived and where I commuted to work, while pursuing my degree at Howard University in nearby Washington, D.C.).

The months that followed the February 2001 announcement would be defined by as much scientific evangelism as you will ever see. The claims? That the completion of a draft of the human genome was our moon landing, our generations moment when we transcended possibility, forever saw the universe in a different light.

But while this hyper-optimism certainly lived in the vapors of the NIH campus, it didnt follow me into the laboratory where I worked.

My advisor, Susan Gottesman, barely spoke of the announcement. Not because she denied its importance, but rather, because she had other things to do and think about.

Her research program almost functioned as the anti-announcement: she studied gene regulation in Escherichia coli, the most unpretentious of model systems. Biology didnt operate further from the spectacle of human biology than the vagaries of E. coli and phage genetics. But these were her instruments, where shed built an international reputation for genetic approaches to understanding how proteins are managed inside of cells, how microbes respond to stressful environments.

Rather than grand statements about what understanding a genome could do in a fight against superbugs across the universe, Gottesman would speak directly about how studying single sets of genes, in a single species of bacteria (E. coli) could tell us about the quirks of microbial metabolism and physiology, how they operated like a board of modules and switches.

So detailed and pure in thought was she that she barely made reference to disease in her work, even though her discoveries absolutely applied to pathogenic organisms (for example, the small regulatory RNAs that she helped to discover in E. coli have now been found to regulate virulence genes in pathogens like Vibrio cholerae).

But her greater gospel, that I learned by osmosis (we didnt talk much about matters not directly about the work), is that the details matter at least as much as the hifalutin concepts do.

This was an important spirit to be around at that time. I was a college activist, who was consuming and reciting big ideas in the genus of social justice (ideas I stand behind, even today). My favorite writers were James Baldwin and Stephen Jay Gould, both authors of bold and beautiful manifestos (even in short essay form).

And it was all of these forces, a nonlinear mix of nature and nurturemy politics, my background (a young, financially disadvantaged African American, raised in a single parent home), and the environments in which my scientific ethics were madethat made me a natural skeptic of big announcements, big pronouncements and scientific grandstanding.

And yes, this included the notion that the draft of the human genome was our moon landing.


After Interviewer Zs advice on how to win, I tried my hand at offering a real response in the form of a question.

Given recent events, did they plan on pivoting away from the study of adenovirus-associated viral vectors for delivering gene therapy? I asked it with a rebellious buzz in my chest, but it was a perfectly reasonable question.

In September 1999, roughly two years before that interview, a young person named Jesse Gelsinger had died while enrolled in a clinical trial for gene therapy run by the University of Pennsylvania. Gelsingers death had a large effect on me: we were close in age, and his death happened less than two years after the release of Gatttaca, a film about a perilous future defined by genetic discrimination.

Since the Gelsinger death, I had noticed a subtle signature of virology programslike the one run by Interviewer Zmigrating away from a gene-therapy focus vectors and into other areas of virus biology.

The brand of gene therapy that had been in voguenear the turn of the millenniumwas one where the corrected form of genes were delivered to the site of interest using viral vectors. Thousands of viruses have evolved machinery to integrate their DNA into their hosts. The logic followed that this aspect of viruses, where they can deliver genes to certain parts of the host genome, could be manipulated for our own goodwe can fix gene variants associated with disease. And after some early promising results, clinical trials were set up to test this in patients.

Gelsinger died during a clinical trial to cure ornithine transcarbamylase deficiency, a genetic condition that he suffered from. After injection with an adenovirus vector, Gelsingers body mounted a large immune response against the virus, which led to a cascade of events culminating in his death.

The Gelsinger death, combined with my personality, experiences and developing ethics, was the reason that the announcement of the completion of the first draft didnt land on me the way it did many others. I had already seen big ideas in science rise and fall.

Twenty years later, I can say that some of my skepticism was poorly founded and misguided. I can proudly admit that almost every field of biology has been irreversibly changed, if not revolutionized, by technology that sprung from that announcement.

We now understand more about the origins of species, the ones that Darwin speculated on, than we ever have.

We have almost real-time outbreak pictures of bacterial and viral genomes creeping through sequence space, sometimes landing on jackpot solutions that facilitate adaptations (but more often landing nowhere, and quite often, off a cliff towards genetic doom).

Genomic technologies driven by the announcement allow us to assess our risk for many important diseases and afflictions.

We can even quantify, to some degree, the magical biodiversity that populates our planet.

The completion of the draft of the human genome helped to democratize the technology, through making genomic sequencing more affordable. You no longer need to study a well-funded human genetic disease in order to afford the tools to sequence and analyze DNA. People who study rainbow trout use genomics. People who study archaea use genomics.

But while some of my young takes might have been sophomoric, others were mature and responsible (even wise).

Among the central messages during the last two decades of genomic science is that the relationship between genotype and phenotype does not function like the pieces of a puzzle. Genes and mutations speak to each other and the environments in which they operate, in surprising ways that defy any existing analogies.

Weve learned that resolving phylogenetic relationships between species and organisms can be a nightmare because biology doesnt operate according to the categories that make it easy to understand. (To put this in perspective, we cant even agree on the very basics, like whether there are two or three domains of life)

Weve learned that genes for disease A often dont cause disease at all. And paradoxically, many people with disease A dont have any identifiable genetic predisposition.

And Homo sapiens? Were an even messier story than we ever predicted: not only are social ideas like race unhelpful for understanding anything essential about the species, they are plainly in the way of a full grasp of the increasingly complex picture of our true origins. Genes from several nonhuman species are peppered throughout our genomes in nontrivial amounts, telling a story of wanderlust and widespread copulation.

As it turns out, my education about the rules of biology over the past two decades has functioned a lot like my education about the rules of real life.

With regard to the latter, there are truths that I can and will hold onto: nice people are great. Greed is bad, and so is racism.

But life isnt that simple.

Because Ive also learned that some people are mean for a reason, greed might happen by accident, and maybe weve all been raised to be bigoted in one way or another. Ive learned the challenge and joy in being empathetic, recognizing our privileges, and dealing with our own biases.

Similarly, DNA is the most fascinating and important string of information in the universe. It tells powerful stories about this bizarre collection of matter that we call life on earth. And it is a privilege to be a part of the species that can study and discuss what it is and how it works.

But it isnt everything. Because life isnt that simple.

And this is what Interviewer Z has since learned. Opportunism around big announcements didnt land them where they hoped. And ironically, the discovery that created the modern face of genetic modification and was awarded a Nobel Prize in 2020CRISPRwas the product of tinkering in microbes in a manner that resembled Susan Gottesmans methods, more than it did Interviewer Zs Art of War tactics.

Months after the interview, I would begin a two-decade-long scientific adventure, where Ive since engaged insect ecology, medicine, biophysics, evolutionary biology and othersalmost entirely (I believe) based on inspiration.

I have landed as an academic who runs my own research program in infectious disease, and am not much younger today than Interviewer Z was at the time of our 2001 interview.

But the advice I give young people today is much different than theirs:

Who the hell knows where the next big discovery will come from? Just hustle and flow, enjoy learning, and ignore the fads and big announcements.

The Human Genome and the Making of a Skeptical Biologist - Scientific American


Breast Cancer Gene Mutations Found in 30% of All Women – Medscape

Monday, February 1st, 2021

New findings of breast cancer gene mutations in women who have no family history of the disease offer a new way of estimating risk and may change the way in which these women are advised on risk management.

The findings come from two large studies, both published on January 20 in The New England Journal of Medicine.

The two articles are "extraordinary" for broadening and validating the genomic panel to help screen women at risk for breast cancer in the future, commented Eric Topol, MD, professor of molecular medicine, Scripps Research, La Jolla, California, and Medscape editor-in-chief.

"Traditionally, genetic testing of inherited breast cancer genes has focused on women at high risk who have a strong family history of breast cancer or those who were diagnosed at an early age, such as under 45 years," commented the lead investigator of one of studies, Fergus Couch, PhD, pathologist at the Mayo Clinic, Rochester, Minnesota.

"[Although] the risk of developing breast cancer is generally lower for women without a family history of the disease...when we looked at all women, we found that 30% of breast cancer mutations occurred in women who are not high-risk," he said.

In both studies, mutations or variants in eight genes BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 were found to be significantly associated with breast cancer risk.

However, the distribution of mutations among women with breast cancer differed from the distribution among unaffected women, notes Steven Narod, MD, from the Women's College Research Institute, Toronto, Ontario, Canada, in an accompanying editorial.

"What this means to clinicians, now that we are expanding the use of gene-panel testing to include unaffected women with a moderate risk of breast cancer in the family history, is that our time will increasingly be spent counseling women with CHEK2 and ATM mutations," he writes. Currently these two are "clumped in with 'other genes'.... [M]ost of the pretest discussion is currently focused on the implications of finding a BRCA1 or BRCA2 mutation."

The new findings may lead to new risk management strategies, he suggests. "Most breast cancers that occur in women with a mutation in ATM or CHEK2 are estrogen receptor positive, so these women may be candidates for anti-estrogen therapies such as tamoxifen, raloxifene, or aromatase inhibitors," he writes.

Narod observes that for now, the management of most women with either mutation will consist of screening alone, starting with MRI at age 40 years.

The medical community is not ready yet to expand genetic screening to the general population, cautions Walton Taylor, MD, past president of the American Society of Breast Surgeons (ASBrS).

The ASBrS currently recommends that all patients with breast cancer as well as those at high risk for breast cancer be offered genetic testing. "All women at risk should be tested, and all patients with pathogenic variants need to be managed appropriately it saves lives," Taylor emphasized.

However, "unaffected people with no family history do not need genetic testing at this time," he told Medscape Medical News.

As to what physicians might do to better manage patients with mutations that predispose to breast cancer, Taylor said, "It's surprisingly easy."

Every genetic testing company provides genetic counselors to guide patients through next steps, Taylor pointed out, and most cancer patients have nurse navigators who make sure patients get tested and followed appropriately.

Members of the ASBrS follow the National Comprehensive Cancer Network guidelines when they identify carriers of a pathogenic variant. Taylor says these are very useful guidelines for virtually all mutations identified thus far.

"This research is not necessarily new, but it is confirmatory for what we are doing, and that helps us make sure we are going down the right pathway," Taylor said. "It confirms that what we think is right is right and that matters," he reaffirmed.

The study led by Mayo's Couch was carried out by the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. It involved analyzing data from 17 epidemiology studies that focused on women in the general population who develop breast cancer. For the studies, which were conducted in the United States, pathogenic variants in 28 cancer-predisposition genes were sequenced from 32,247 women with breast cancer (case patients) and 32,544 unaffected women (control persons).

In the overall CARRIERS analysis, the prevalence of pathogenic variants in 12 clinically actionable genes was 5.03% among case patients and 1.63% among control persons. The prevalence was similar in non-Hispanic White women, non-Hispanic Black women, and Hispanic case patients, as well as control persons, they add. The prevalence of pathogenic variants among Asian American case patients was lower, at only 1.64%, they note.

Among patients who had breast cancer, the most common pathogenic variants included BRCA2, which occurred in 1.29% of case patients, followed by CHEK2, at a prevalence of 1.08%, and BRCA1, at a prevalence of 0.85%.

Mutations in BRCA1 increased the risk for breast cancer more than 7.5-fold; mutations in BRCA2 increased that risk more than fivefold, the investigators state.

Mutations in PALB2 increased the risk of breast cancer approximately fourfold, they add.

Prevalence rates for both BRCA1 and BRCA2 among breast cancer patients declined rapidly after the age of 40. The decline in other variants, including ATM, CHEK2, and PALB2, was limited with increasing age.

Indeed, mutations in all five of these genes were associated with a lifetime absolute risk for breast cancer greater than 20% by the age of 85 among non-Hispanic Whites.

Pathogenic variants in BRCA1 or BRCA2 yielded a lifetime risk for breast cancer of approximately 50%. Mutations in PALB2 yielded a lifetime breast cancer risk of approximately 32%.

The risk of having a mutation in specific genes varied depending on the type of breast cancer. For example, mutations in BARD1, RAD51C, and RAD51d increased the risk for estrogen receptor (ER)negative breast cancer as well as triple-negative breast cancer, the authors note, whereas mutations in ATM, CDH1, and CHEK2 increased the risk for ER-positive breast cancer.

"These refined estimates of the prevalences of pathogenic variants among women with breast cancer in the overall population, as opposed to selected high-risk patients, may inform ongoing discussions regarding testing in patients with breast cancer," the BCAC authors observe.

"The risks of breast cancer associated with pathogenic variants in the genes evaluated in the population-based CARRIERS analysis also provide important information for risk assessment and counselling of women with breast cancer who do not meet high-risk selection criteria," they suggest.

The second study was conducted by the Breast Cancer Association Consortium (BCAC) under lead author Leila Dorling, PhD, University of Cambridge, United Kingdom. This group sequenced 34 susceptibility genes from 60,466 women with breast cancer and 53,461 unaffected control persons.

"Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2 and PALB2) were associated with a significant risk of breast cancer overall (P < .0001)," the BCAC members report. "For these genes, odds ratios ranged from 2.10 to 10.57," they add.

The association between overall breast cancer risk and mutations in seven other genes was more modest, conferring approximately twice the risk for breast cancer overall, although that risk was threefold higher for the TP53 mutation.

For the 12 genes the consortium singled out as being associated with either a significant or a more modest risk for breast cancer, the effect size did not vary significantly between European and Asian women, the authors note. Again, the risk forER-positive breast cancer was over two times greater for those who had either the ATM or the CHEK2 mutation. Having mutations in BARD1, BRCA1, BRCA1, PALB2, RAD51C, and RAD51D conferred a higher risk for ER-negative disease than for ER-positive disease.

There was also an association between rare missense variants in six genes CHEK2, ATM, TP53, BRCA1, CDH1, and RECQL and overall breast cancer risk, with the clearest evidence being for CHEK2.

"The absolute risk estimates place protein-truncating variants in BRCA1, BRCA2, and PALB2 in the high-risk category and place protein-truncating variants in ATM, BARD1, CHEK2, RAD51CC, and RAD51D in the moderate-risk category," Dorling and colleagues reaffirm.

"These results may guide screening as well as prevention with risk-reducing surgery or medication, in accordance with national guidelines," the authors suggest.

The CARRIERS study was supported by the National Institutes of Health. The study by Dorling and colleagues was supported by the European Union Horizon 2020 research and innovation programs, among others. Narod has disclosed no relevant financial relationships.

New Eng J Med. Published online January 20, 2021. Couch et al, Abstract; BCAC study, Full text; Editorial

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Breast Cancer Gene Mutations Found in 30% of All Women - Medscape


Mysterious untreatable fevers once devastated whole families. This doctor discovered what caused them – CNN

Monday, February 1st, 2021

They couldn't explain why those afflicted, often in the same family, had recurring fevers, abdominal pain, troublesome rashes and muscle aches. Known as familial Mediterranean fever, the disease often went undiagnosed for years, and it was sometimes fatal.

A similar, but unrelated, mystery fever was initially thought to affect families with Scottish and Irish heritage.

"The pain I felt back then, it moved around. One week the pain was in my leg, and the next week my arm would hurt instead," said Victoria Marklund, 47, a Swedish woman who suffered from TRAPS, or tumor necrosis factor receptor-associated periodic syndrome, a disease first identified in a family of Irish and Scottish descent living in the UK city of Nottingham in 1982.

Her father and grandfather died prematurely from kidney complications, which were likely a consequence of the undiagnosed disorder.

Marklund has now received an effective treatment and lives symptom-free -- largely thanks to the work of one US physician and health researcher, Dr. Dan Kastner, a distinguished investigator at the National Institutes of Health who serves as scientific director of the National Human Genome Research Institute.

"What Dr. Kastner has accomplished is absolutely groundbreaking. The concept of autoinflammatory disorders didn't exist before he identified the cause behind a number of them," said Olle Kmpe, a professor of clinical endocrinology at Karolinska Institutet in Stockholm who is a member of The Royal Swedish Academy of Sciences and chair of the Prize Committee. The academy also selects Nobel laureates.

"His discoveries have taught us a great deal about the immune system and its functions, contributing to effective treatments that reduce the symptoms of disease from which patients previously suffered enormously," Kmpe added.


Kastner first came across familial Mediterranean fever in a patient with recurring arthritis and high fevers he treated as a rheumatology fellow just months into his first job at the NIH in Bethesda, Maryland, in 1985. That chance diagnosis set him on a 12-year journey to find the gene -- or genes -- responsible for the disease.

"It was known that familial Mediterranean fever was a genetic disease. It was known that it was recessively inherited, but no one knew what the gene was, or even the chromosome," he said.

He traveled to Israel, where he took blood samples from 50 families with familial Mediterranean fever.

It took Kastner seven years to locate the mutation to chromosome 16. It took another five years -- in 1997 -- for Kastner and his team to find the mutated gene itself -- one misprint in a genetic code comprised of 3 billion letters.

After this breakthrough, he stayed at NIH, where he studied undiagnosed patients with similar symptoms. He identified 16 autoinflammatory genetic disorders and found effective treatments for at least 12 of them, establishing a whole new field of medicine.

Now that the full human genome has been mapped, the process of detecting the genetic root of such disorders is quicker, and greater numbers of patients with these rare, unexplained diseases are being helped as a result of Kastner's work.


There are few images in science more iconic than the DNA double helix structure, discovered in 1953 by James Watson and Francis Crick, two years after Kastner was born. As a seventh grader, he once created a version of the twisted ladder shape using jelly beans and pipe cleaners for a science fair.

His work to identify the gene that caused familial Mediterranean fever had its own element of competition. In the summer of 1997, to beat a rival team led by French researchers, Kastner took a last-minute flight from Bethesda, Maryland, where the NIH is based, to Boston to submit his manuscript detailing the gene mutation that caused familial Mediterranean fever by hand to the journal Cell on a Friday afternoon.

These were the days before papers could be submitted with the click of a mouse. He hoped to publish his work first. Ultimately, the two teams published their papers simultaneously in different journals -- both fortunately arriving at the same finding.

"I love that type of thing," he said. "We still have races to the finish, and there's nothing like a good week of all-nighters."

Kastner had discovered that the gene involved in familial Mediterranean fever produces a protein called pyrin. Normally this helps to activate our innate immune system -- our first line of defense to fight bacteria and viruses.

In this case, however, pyrin made the innate immune system become overactive, resulting in fever, pain and joint inflammation. He went on to study patients with similar and more devastating symptoms -- identifying TRAPS and many more rare diseases.

Transforming lives

What has motivated Kastner for five decades is how his work decoding the genetics of inflammation can inform new treatments and ultimately transform patients' lives.

"There's nothing more gratifying in life and nothing more satisfying scientifically," he said. He plans to step down from his role as scientific director at the NIH in the next few months and then focus his efforts on his clinic, where he has over 3,000 patients enrolled and "find yet more disease genes, understand how they work, and develop new treatments."

"Of course, one can never know how long that will last, but I love doing it, and will continue as long as I can."

In more recent work beginning in 2014, Kastner identified and pioneered treatment for a severely debilitating genetic disorder known as DADA2, short for deficiency of the enzyme ADA2 (adenosine deaminase 2), which can cause recurring fevers and strokes starting in childhood. His research has radically improved the life of the daughter of Dr. Chip Chambers.

"She's now at college and the improvement in her quality of life has been dramatic."

Similarly, TRAPS survivor Marklund suffered for years before her diagnosis at the age of 38. Her nephews, who both have TRAPS but have been given medicine from an early age, don't feel the effects of the disease at all, she told The Royal Swedish Academy Of Sciences.

"I doubted many times that anyone would ever figure out what I was suffering from. So now it feels fantastic, to be told what it was, to understand the cause of the disease and that there is medicine that helps."

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Mysterious untreatable fevers once devastated whole families. This doctor discovered what caused them - CNN


CCMB team identifies variants of genes that metabolise drugs – BusinessLine

Monday, February 1st, 2021

As India emerges a destination of global choice for clinical trials of various drugs, a study on variants of the gene important for drug metabolism seeks to explore how drugs function across diverse populations.

Dr K Thangaraj and his team from CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad, recently published their study of diversity of cytochrome-P450-2C9 (CYP2C9) gene in Pharmacogenomics and Personalized Medicine.

Healthcare is now moving towards personalised medicine. Our studies on the genetic diversity of India will play an important role in this transition, says Dr Rakesh Mishra, Director, CCMB.

The study is important as it seeks to analyse doctor-prescribed dose of drugs based on the gender, age and body mass index (BMI) of patients. However, there are hypersensitive response like rashes, vomiting and nausea.

Individuals in a population have variations in their genes needed for metabolism of a wide range of drugs. Any changes in the sequence of gene may affect the production of protein in human liver. This can cause slower metabolism of a drug and slower or reduced rate of excretion. Many of these drugs have a narrow therapeutic index they are tolerated by human bodies in very specific amounts, according to scientists.

When these drugs are retained in the body for longer, that can lead to toxicity. So, it is important to decide the right dosage for each individual depending on the sequence of their CYP2C9 gene.

Dr Thangarajs team studied the diversity of this gene among 1,488 Indians across 36 population groups, representing different linguistic groups, castes and tribes, among other parameters. They also looked into genes of 1,087 individuals from other countries of South Asia. We found eight new variants of the CYP2C9 gene, making a total of 11 known variants of the gene in South Asia, says Dr Nizamuddin, who is the first author in the study.

They find no correlation between any of these variants with the linguistic and geographical population groups. However, a few Indian populations have more than 20 per cent people with a deleterious variant of the gene. Those with this variant are at a disadvantage in their ability to metabolise drugs. The eight new variants found in this study are also predicted to have similar effect on drug metabolism.

It is important to know the variations in the CYP2C9 gene to help medical practitioners decide the right dosage of medicine for each patient. The knowledge of this variation will also be important for conducting more meaningful clinical trials. This study also suggests that it might not be the best thing to conduct a common clinical trial for the entire world. We need population-specific trials, says Dr Thangaraj, the corresponding author of this paper and presently Director of the Centre for DNA Fingerprinting and Diagnostics (CDFD), Hyderabad.

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CCMB team identifies variants of genes that metabolise drugs - BusinessLine


NeuBase Therapeutics Announces Acquisition of Gene Modulating Technology from Vera Therapeutics – GlobeNewswire

Monday, February 1st, 2021

Acquisition includes intellectual property for peptide nucleic acid genetic medicine portfolio that has demonstrated in vivo activity in several disease indications

Consolidates new peptide nucleic acid technology into NeuBases PATrOL platform

Extends the ability of NeuBases existing technology to directly modulate the human genome with high precision to resolve rare and common diseases, including cancers

PITTSBURGH, Jan. 28, 2021 (GLOBE NEWSWIRE) -- NeuBase Therapeutics, Inc. (Nasdaq: NBSE) ("NeuBase" or the "Company"), a biotechnology company accelerating the genetic revolution using a new class of synthetic medicines to drug the genome, today announced execution of a binding agreement to acquire infrastructure, programs and intellectual property for several peptide-nucleic acid (PNA) scaffolds from Vera Therapeutics, formerly known as TruCode Gene Repair, Inc. The technology has demonstrated the ability to resolve disease in genetic models of several human indications. The acquisition bolsters NeuBases capabilities and reinforces the Companys position as a leader in the field of genetic medicine.

"With this acquisition, we enhance our PATrOL platform, furthering our unique ability to directly engage and correct malfunctioning genes with exquisite precision to address the root causes of a wide variety of human diseases, said Dietrich A. Stephan, Ph.D., Chief Executive Officer of NeuBase. These assets extend and refine our PATrOL platforms capabilities and accelerates, through our Company, to bring the rapidly growing genetic medicines industry toward a single high-impact focal point. We are committed to advancing our pipeline and candidates to the clinic and to exploiting the full potential of PNA technology to continue creating value for our shareholders and importantly, for patients."

Curt Bradshaw, Ph.D., Chief Scientific Officer of NeuBase, added, "By consolidating additional validated technology into our PATrOL platform, we believe NeuBase is positioned to radically transform the landscape of medicine. In vivo activity in a variety of disease indications has been demonstrated with the new scaffolds that we have acquired, and further expands the validated components of our platform to achieve resolution of causality in living systems with target indications such as recently presented in myotonic dystrophy, type 1. In addition to our intellectual property, we believe our in-house expertise in peptide nucleic acids is second to none.

The transaction is expected to close in the first calendar quarter of 2021. Financial terms were not disclosed.

About NeuBase Therapeutics, Inc.NeuBase is leading the genetic revolution using a new class of synthetic medicines. NeuBase's designer PATrOL therapies are centered around its proprietary drug scaffold to address genetic diseases at the source by combining the highly targeted approach of traditional genetic therapies with the broad organ distribution capabilities of small molecules. With an initial focus on debilitating neurological, neuromuscular and oncologic disorders, NeuBase is committed to redefining medicine for the millions of patients with both common and rare conditions. The companys current portfolio of high value programs includes myotonic dystrophy, type 1 and Huntingtons disease. To learn more, visit

Use of Forward-Looking StatementsThis press release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act. These forward-looking statements are distinguished by use of words such as "will," "would," "anticipate," "expect," "believe," "designed," "plan," or "intend," the negative of these terms, and similar references to future periods and include, among other statements, those related to the anticipated benefits of the acquisition of assets from Vera Therapeutics and the expected closing date of the transaction. These views involve risks and uncertainties that are difficult to predict and, accordingly, our actual results may differ materially from the results discussed in our forward-looking statements. Our forward-looking statements contained herein speak only as of the date of this press release. Factors or events that we cannot predict, including those risk factors contained in our filings with the U.S. Securities and Exchange Commission, may cause our actual results to differ from those expressed in forward-looking statements. The Company may not actually achieve the plans, carry out the intentions or meet the expectations or projections disclosed in the forward-looking statements, and you should not place undue reliance on these forward-looking statements. Because such statements deal with future events and are based on the Company's current expectations, they are subject to various risks and uncertainties, and actual results, performance or achievements of the Company could differ materially from those described in or implied by the statements in this press release, including: the risk that the Company does not achieve the anticipated benefits from the acquisition of assets from Vera Therapeutics; risks that the conditions to closing the transaction are not met and the transaction does not close; the Company's plans to develop and commercialize its product candidates; the timing of initiation of the Company's planned clinical trials; the timing of the availability of data from the Company's clinical trials; the timing of any planned investigational new drug application or new drug application; the Company's plans to research, develop and commercialize its current and future product candidates; the clinical utility, potential benefits and market acceptance of the Company's product candidates; the Company's commercialization, marketing and manufacturing capabilities and strategy; global health conditions, including the impact of COVID-19; the Company's ability to protect its intellectual property position; and the requirement for additional capital to continue to advance these product candidates, which may not be available on favorable terms or at all, as well as those risk factors contained in our filings with the U.S. Securities and Exchange Commission. Except as otherwise required by law, the Company disclaims any intention or obligation to update or revise any forward-looking statements, which speak only as of the date hereof, whether as a result of new information, future events or circumstances or otherwise.

NeuBase Investor Contact:Dan FerryManaging DirectorLifeSci Advisors, OP: (617) 430-7576

NeuBase Media Contact:Cait Williamson, Ph.D.LifeSci OP: (646) 751-4366

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NeuBase Therapeutics Announces Acquisition of Gene Modulating Technology from Vera Therapeutics - GlobeNewswire


Copy number variations linked to autism have diverse but overlapping effects – Spectrum

Monday, February 1st, 2021

Mapping outcomes: Some genetic mutations can lead to a wide variety of traits, including those associated with autism.

People with mutations in distant chromosomal regions often share a range of autism traits, even if they do not meet the diagnostic threshold for autism, according to a new study.

Mutations called copy number variations (CNVs) involve duplications or deletions of large stretches of DNA. Having a CNV in the 16p11.2 or 22q11.2 chromosomal region increases a persons likelihood of being diagnosed with autism, but previous studies have found significant variability in the traits associated with mutations in either location.

The new work shows that deletions or duplications in 16p11.2 or 22q11.2 track with distinct profiles of cognitive abilities and autism traits, and that each type of variant is linked to a different probability of being diagnosed with autism.

These profiles overlap, which suggests that the different CNVs have similar impacts on developmental pathways involved with autism, says lead investigator Marianne van den Bree, professor of psychological medicine at Cardiff University in the United Kingdom. The findings also support the idea that other factors such as the environment or other genes shape a persons autism traits.

Van den Bree and her colleagues across eight institutions pooled data from 547 people with a deletion or duplication in 16p11.2 or 22q11.2. They compared the data with similar information from the Autism Genome Project, looking at 2,027 autistic people who do not have these CNVs.

Pulling these datasets together provided an in-depth look at patterns of outcomes. The four groups of people with CNVs a deletion or duplication in either chromosomal region differ the most in motor function, van den Bree and her colleagues found. And people with 22q11.2 deletions are less likely to have an autism diagnosis than those with any of the other CNVs, but they still have a higher autism prevalence than the general population.

People with a duplication in 22q11.2 or 16p11.2 tend to have more severe autism traits than people with deletions, the researchers found. And people with a 16p11.2 duplication or 22q11.2 deletion have greater cognitive impairment than those with one of the other two variants do.

Despite these differences between groups, people within each group show even greater variability, the team found, which suggests that other factors contribute to a persons traits. The work appeared in January in the American Journal of Psychiatry.

These four CNVs have not previously been compared in this way, but the study feels more confirmatory than it feels like its carving out something new, says Elliott Sherr, professor of neurology at University of California, San Francisco, who was not involved in the new work.

Many people, however, including some clinicians, are unaware that these genetic conditions are often linked to autism, says study investigator Samuel Chawner, research fellow in psychology at Cardiff University. He says he hopes that the profiles he and his colleagues identified will inform how genetic conditions are treated. For instance, 54 percent of people carrying one of the CNVs who do not have an autism diagnosis still have significant autism-like difficulties.

Whats missing from the new work is an examination of what else besides the CNVs contributes to the diversity of traits seen in people with these mutations, such as environment and other genes, says David Ledbetter, chief clinical officer at Dascena, a personalized medicine company. Ledbetter was not involved in the study.

For example, people with a 22q11.2 deletion have an increased likelihood of having schizophrenia, but information from the rest of their genome can help to accurately forecast outcomes, according to a study published in November. This same technique could be used to predict traits in people with the other CNVs, Ledbetter says.

A persons environment including their ability to access medical support and early education may also play a role in this variability, Chawner says. Van den Bree, Chawner and their colleagues at the Genes to Mental Health consortium plan to study how these factors in particular contribute to traits in people with CNVs.

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Copy number variations linked to autism have diverse but overlapping effects - Spectrum


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