Promising Drug Candidate Reverses Serious Heart Disease Associated with Noonan Syndrome

Research published in the premier journal, Circulation, points to a potential new treatment for children and families affected by rare genetic heart disease.

Scientists at Masonic Medical Research Institute (MMRI), in collaboration with Mount Sinai Health System in New York City, have identified a promising drug candidate that reverses a severe form of heart disease linked to Noonan syndrome, a rare genetic disorder that often affects infants and children. The findings, co-led by Maria I. Kontaridis, Ph.D., Executive Director, Gordon K. Moe Professor and Chair of Biomedical Research and Translational Medicine and Director of Research at MMRI, and Bruce D. Gelb, M.D., Dean for Child Health Research, Icahn School of Medicine at Mount Sinai and The Gogel Family Chair and Director of The Mindich Child Health and Development Institute at Mount Sinai Health System, have been accepted for publication in Circulation, one of the world’s leading cardiovascular journals.

Noonan syndrome is one of a group of rare genetic disorders known as RASopathies. About one in five people with this syndrome develop hypertrophic cardiomyopathy (HCM), a condition in which the heart muscle becomes dangerously thick, making it harder for the heart to pump blood. There are currently no approved treatments that can reverse this form of heart disease.

In the study, researchers found that treatment with rigosertib reversed heart muscle thickening, restored heart function, and normalized disease-associated changes. The treatment also improved other features of Noonan syndrome, including bone growth and facial development, suggesting it may benefit multiple aspects of the disorder.

The research also showed that rigosertib outperformed another drug currently being explored for Noonan syndrome, yielding greater improvements in cardiac structure and function. Because rigosertib has already been studied in people for other diseases, researchers hope it could move more quickly toward future clinical studies for those with this disorder.

“Hypertrophic cardiomyopathy is one of the most serious complications of Noonan syndrome, and families currently have very few treatment options,” said Maria I. Kontaridis, Ph.D., Executive Director of MMRI and senior co-corresponding author of the study. “Our findings show that rigosertib not only slowed the disease but actually reversed existing heart damage. While more research is needed before this approach can be tested in patients, these results represent an exciting step toward a treatment that addresses the underlying cause of HCM in this disease.”

MMRI staff who contributed to this paper include: Maria I. Kontaridis, Ph.D.; Levi Legler, Ph.D.; Bing Xu, Ph.D.; Chase Kessinger, Ph.D.; Izabella Vredenburg; Yan Sun, Ph.D.; Frank A. Dinenno, Ph.D.; and Damian Bohler.

Read the full publication HERE.