MDA, FARA fund grant to study heart fibrosis in FA
Weill Cornell, Indiana University researchers aim to ID drivers
A newly awarded $300,000 research grant will fund a study on heart fibrosis, or the accumulation of scar tissue, in people with Friedreich’s ataxia (FA).
The Muscular Dystrophy Association (MDA) and Friedreich’s Ataxia Research Alliance (FARA) awarded the grant to researchers at Weill Cornell Medical Center and Indiana University. Their project, titled “Molecular and Cellular Mechanisms of Cardiac Fibrosis in Friedreich Ataxia,” aims to identify early drivers of heart damage and fibrosis and reveal potential therapeutic targets.
“This grant reflects our strategic priority to support research that addresses the full impact of FA, including its most devastating manifestations in the heart,” Angela Lek, PhD, interim chief research officer at MDA, said in an association press release. “By better understanding the mechanisms that drive fibrosis, we move closer to meaningful therapeutic interventions for people living with this disease.”
That understanding “is essential not just for prolonging life, but for improving quality of life for individuals with FA,” said Jennifer Farmer, FARA’s CEO.
FA is caused by mutations in the FXN gene that impair the production of frataxin, a protein required for the proper function of mitochondria, cellular structures that produce the energy cells need to function. The mitochondrial dysfunction that occurs in FA results in degeneration of the nerves involved in muscle control.
Heart problems common in FA
Most FA patients develop heart problems, such as enlargement of the heart muscle and accumulation of scar tissue, contributing to the progressive decline of heart function. Over time, patients may develop heart failure, when the heart is no longer able to adequately pump blood out to the body, and alterations in heart rhythm.
“Cardiac complications [remain] one of the most urgent and life-limiting aspects of Friedreich’s ataxia, yet our understanding of how fibrosis develops and progresses, is still incomplete,” Lek said.
The newly funded study will focus on fibroblasts, cells responsible for producing the extracellular matrix (ECM), which provides structural and functional support to the heart. Excessive activation of fibroblasts and ECM deposition leads to fibrosis, impairing heart function.
The researchers will use cellular and mouse models of FA to identify the damaging and potentially compensatory mechanisms involved in cardiomyopathy to unravel measurable biomarkers of heart damage, and to find therapeutic targets to slow or reverse the disease progression.
“By identifying the early triggers of cardiomyocyte [heart muscle cell] injury and fibrotic remodeling, we hope to inform the development of strategies that can intercept the disease process before irreversible damage occurs,” said Giovanni Manfredi, MD, PhD, neuroscience professor at Weill Cornell Medical College and one of the study’s principal investigators.
Co-investigator Anna Stepanova, PhD, research associate at Weill Cornell Medicine, said the scientists are “taking a highly integrative approach, combining cellular models, animal studies, and molecular analyses to map out how fibrosis unfolds in the FA heart.”
“This funding allows us to focus on the fundamental biology that drives these cardiac changes and to explore how we can leverage that knowledge to develop more effective treatments,” said R. Mark Payne, MD, a professor at Indiana University School of Medicine and the study’s other principal investigator
MDA and FARA have been collaborating to fund high-impact studies and accelerate breakthroughs for people with FA.
“As someone with two sons living with FA, I’ve come to understand that the heart issues can be just as difficult, if not more so, than the mobility challenges,” said MDA family member Tom Henry. “Knowing that researchers are zeroing in on the cause of cardiac fibrosis gives me real hope that treatments are on the horizon that could change our futures.”
