Genetics key to treating heart muscle disorders: Vanderbilt Prize lecturerSep. 19, 2019, 8:47 AM
by Bill Snyder
Advances in genetics are leading to new ways to treat cardiomyopathies — devastating heart muscle disorders that lead to heart failure, Christine Seidman, MD, recipient of the 2019 Vanderbilt Prize in Biomedical Science, said last week during her Vanderbilt Prize lecture.
Many cases of cardiomyopathy result from genetic mutations affecting key heart muscle proteins, said Seidman, the Thomas W. Smith Professor of Medicine and Genetics at Harvard Medical School and director of the Cardiovascular Genetics Center at the Brigham and Women’s Hospital.
Understanding how these mutations impair heart function has led, in the case of hypertrophic cardiomyopathy, to a novel treatment that currently is being tested in patients.
“For the first time there might be real opportunity to treat these patients,” she said.
Characterized by abnormal thickening of the heart, hypertrophic cardiomyopathy is the most common inherited disease of the heart muscle.
Responsible for most cases of sudden cardiac death among athletes, it is a disease of the sarcomere, the contractile unit of the heart.
Early signs include hypercontractility and impaired relaxation of heart muscle. Studies by Seidman’s group and others have linked the condition to genetic mutations affecting the predominant form of the myosin motor protein in the heart and a myosin-binding protein that modulates cardiac contraction.
These mutant myosin molecules have enhanced enzymatic activity leading to increased energy consumption. That, in turn, fuels hypercontractility, essentially “remodeling” the heart in a way that increases the risk of atrial fibrillation, stroke and heart failure.
Reasoning that “dialing back” contractility could improve the heart’s capacity to relax, Seidman and her colleagues identified a molecule that appears to normalize myosin function.
The potential drug, called mavacamten, is now in Phase II clinical trials led by MyoKardia Inc., a biopharmaceutical company that Seidman co-founded.
Seidman, a Howard Hughes Medical Institute investigator and member of the National Academy of Medicine and National Academy of Sciences, is the 14th recipient of the Vanderbilt Prize.
Established in 2006 by the Vanderbilt University School of Medicine, the prize honors women scientists with a stellar record of research accomplishments who have made significant contributions to mentoring other women in science.
Prize winners mentor women in the School of Medicine who are pursuing graduate studies in the biomedical sciences.
Seidman will mentor this year’s Vanderbilt Prize Scholar, Megan Rasmussen, a doctoral candidate in the Department of Cell and Developmental Biology.
In her opening remarks, Seidman applauded Vanderbilt as “a fabulous medical school.
“It continues to surprise me in being first in everything that matters to me,” she continued, “first in a biobank, first in genetics applied to clinical care — pharmacogenetics in particular — and first in celebrating women in science.”
Seidman’s talk, part of the Flexner Discovery Lecture Series, was sponsored by the offices of the Executive Vice President for Research and Dean of Basic Sciences.