Genomic Medicine Institute

Researchers have identified a common diabetes medication, metformin, as a possible treatment for atrial fibrillation. They used advanced computation and genetic sequencing to determine that metformin's targets overlap significantly with genes dysregulated in atrial fibrillation. Cleveland Clinic researchers have identified a common diabetes medication, metformin, as a possible treatment for atrial fibrillation. The study, published in Cell Reports Medicine, built on ongoing collaborative Cleveland Clinic research to support further investigation into metformin as a drug repurposing candidate. Researchers used advanced computation and genetic sequencing to determine that metformin's targets overlap significantly with genes dysregulated in atrial fibrillation. "Finding drugs or procedures to treat atrial fibrillation is difficult because of potential serious side effects," said Mina Chung, M.D., senior author of the study who is in Cleveland Clinic's Department of Cardiovascular Medicine in the Heart, Vascular and Thoracic Institute. "There is a significant need for new treatments for atrial fibrillation as there have been no new drugs approved in more than a decade." "It's not that we've found a new drug target where it takes 20 years to test this in individuals," said Jessica Castrillon Lal, the study's first author and a fifth-year graduate student in the Cleveland Clinic Molecular Medicine program. "We can cut off 10+ years in the drug development pipeline. We already have the information there. We just have to test it in a very computationally efficient way, such as artificial intelligence technology," said Feixiong Cheng, Ph.D., co-senior author of the study who is Associate Staff at the Genomic Medicine Institute in Cleveland Clinic's Lerner Research Institute. The analysis found metformin targeted 30 genes associated with atrial fibrillation, with direct effects on gene expression for eight. Eight other candidate drugs surfaced in the analysis, but researchers were able to identify metformin as the most promising candidate through testing and reviewing outcomes in large stores of patient data. Castrillon Lal conducts research in Dr. Cheng's lab, which uses network medicine approaches to find candidate drugs for repurposing, creating vast networks of molecular interactions. For this study, researchers winnowed down a list of 2,800 FDA-approved treatments by analyzing three data sources: a map of interactions between proteins called an "interactome"; a network of genes associated with atrial fibrillation; and each medicine's molecular or genetic targets. Atrial fibrillation is the most common type of heart arrhythmia in the world and can lead to complications, including stroke and heart failure. Treatments have been primarily directed toward trying to prevent the arrhythmia using drugs targeting the electrical system, including ion channels in the heart, or using catheter ablation to isolate the pulmonary veins where initiating beats of atrial fibrillation occur. However, side effects, limited success and potential complications can limit these approaches. The research was conducted in collaboration with labs led by Dr. Chung, Dr. Cheng, David Van Wagoner, Ph.D.; Jonathan Smith, Ph.D., Department of Cardiovascular and Metabolic Sciences; and John Barnard, Ph.D., Department of Quantitative Health Sciences in the Lerner Research Institute. Prior work from Drs. Chung, Smith, Van Wagoner, and Barnard had also identified the enzyme AMPK as a potential key regulator for metabolic stress. Metabolic stress has been associated with atrial fibrillation.

RenaCARE Study to Evaluate the Clinical Utility of Renasight in the Diagnosis and Management of Chronic Kidney Disease AUSTIN, Texas, Aug. 11, 2022 /PRNewswire/ -- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, today announced full enrollment for the RenaCARE (Renasight Clinical Application, Review and Evaluation) study, a real world, prospective, multi-center clinical study to assess the clinical utility of Natera's Renasight™ genetic testing panel, which analyzes more than 380 genes related to kidney disease. Enrollment in the study was completed early as a result of statistically meaningful interim data analysis. The study includes more than 1,700 patients across 30+ sites, representing leading academic and private nephrology clinics in the U.S. A publication for the RenaCARE study is expected to be submitted in early 2023. The RenaCARE study aims to demonstrate how genetic findings impact the clinical management of patient care and examines outcomes of patients tested with the Renasight genetic testing panel. It will also assess patient satisfaction, health knowledge and genetic literacy. The study follows a 2019 publication1 in The New England Journal of Medicine showing that approximately 10% of people with chronic kidney disease (CKD) have a genetic diagnosis. "RenaCARE is the only large-scale prospective multi-site study, to our knowledge, looking at the clinical utility of performing routine genetic testing on CKD patients," said Sangeeta Bhorade, M.D., chief medical officer for organ health at Natera. "We're optimistic this study could have the potential to optimize the management of patients with chronic kidney disease and ultimately improve outcomes." Ali Gharavi, M.D., the study's principal investigator, serves as the chief of the Division of Nephrology at New York-Presbyterian/Columbia University Irving Medical Center, director of the Center for Precision Medicine and Genomics in the Department of Medicine, and interim director of the Institute of Genomic Medicine at Columbia University Vagelos College of Physicians and Surgeons. Dr. Gharavi is also a close collaborator with Kidney Disease: Improving Global Outcomes foundation (KDIGO) and the National Kidney Foundation (NKF). About Renasight The Renasight™ test is a germline genetic test that screens for hereditary causes of kidney disease. It is indicated for patients with diagnosed kidney disease and is run from a patient's blood or saliva sample. Providers can use the Renasight test to identify a genetic predisposition, clarify a clinical diagnosis, or identify the etiology of an unknown kidney disease to help inform medical management. Additionally, genetic counseling and familial testing can be offered based on the test result. The test has been developed and its performance characteristics determined by the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the U.S. Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified. About Natera Natera™ is a global leader in cell-free DNA testing, dedicated to oncology, women's health, and organ health. Our aim is to make personalized genetic testing and diagnostics part of the standard of care to protect health and enable earlier and more targeted interventions that help lead to longer, healthier lives. Natera's tests are validated by more than 100 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit . Forward-Looking Statements All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera's plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera's expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our screening tests, or of the benefits of our screening tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera's recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at and . Contacts Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350 Media: Brian Symmons, SVP of Marketing and Corporate Affairs, Natera, Inc., pr@natera.com References Groopman EE, Marasa M, Cameron-Christie S, et al. Diagnostic Utility of Exome Sequencing for Kidney Disease. N Engl J Med. 2019; 380:142-151 DOI: 10.1056/NEJMoa1806891 Company Codes: NASDAQ-NMS:NTRA

A new study has identified geographic patterns of high and low mortality rates of young-onset colorectal cancer (yoCRC) in the United States. The findings will contribute to improved understanding of the underlying drivers of yoCRC mortality and may help to guide policy discussions surrounding screening guidelines and region-specific interventions. A new study led by Lerner Research Institute and the Center for Young-Onset Colorectal Cancer at Cleveland Clinic has identified geographic patterns of high and low mortality rates of young-onset colorectal cancer (yoCRC) in the United States, according to a research letter published in Gastroenterology. The findings will contribute to improved understanding of the underlying drivers of yoCRC mortality and may help to guide policy discussions surrounding screening guidelines and region-specific interventions. "Incidence and mortality of yoCRC, defined as colorectal cancer occurring in individuals under the age of 50, have been steadily increasing since the mid-1990's, but we still do not understand why," said the study's senior author Stephanie Schmit, PhD, MPH, Vice Chair of the Genomic Medicine Institute. "With this study, we aimed to establish where yoCRC mortality rates were higher or lower than expected, known as hot and cold spots, in order to pinpoint regions in the country warranting further investigation and to understand the factors contributing to this increasing burden." In this study, the researchers utilized colorectal cancer-specific mortality data from 3,036 U.S. counties between 1999 and 2019. The geospatial clustering models were adjusted for yoCRC risk factors and prognostic indicators, including age, sex, race/ethnicity, obesity, smoking, alcohol consumption and socioeconomic conditions. They specifically assessed two broad age-at-diagnosis categories of younger than 50 and older than 50 as well as four stratified categories of younger than 35, 35 to 49, 50 to 64 and older than 65. Notably, they discovered new mortality hot spots in the Midwest/northeastern Great Lakes region, which constitutes the first reporting of yoCRC mortality hot spots in these areas, in addition to cold spots in western/southwestern counties that have lower risk of yoCRC death. They also found mortality hot spots in southern and Appalachian counties in the younger than 50 category that were consistent with previous studies. However, they determined that hot spots among those ages 35 to 49 more closely followed southern patterns seen in average-onset CRC while hot spots in those younger than age 35 did not, which suggests that deaths among the youngest yoCRC patients may be driven by a distinct set of factors. "While we recognize that unmeasured factors, such as access to care and related treatment disparities, may be influencing our study results, our findings may initiate new research examining yoCRC mortality-related factors specific to region and age, such as healthcare system accessibility or diet, and provide an impetus to target interventions in particular regions," said R. Blake Buchalter, PhD, MPH, the study's first author. Dr. Buchalter is a postdoctoral fellow in Dr. Schmit's lab and the lab of Jesse Schold, PhD, in the Department of Quantitative Health Sciences. His fellowship is supported by the Computational Genomic Epidemiology of Cancer (CoGEC) National Cancer Institute-funded T32 Training Program at Case Western Reserve University.