Heart disease remains a major cause of illness and mortality in Friedreich’s ataxia. Growing evidence suggests that, in addition to mitochondrial dysfunction, abnormal activation of the immune system may contribute to cardiac damage. When mitochondria become damaged, they can release mitochondrial DNA into the cell, where it may be mistaken for a sign of infection and trigger inflammation, heart muscle cell death, and cardiomyopathy.
Dr. Gaomin Feng will investigate an immune signaling pathway involving Z-DNA-binding protein 1 (ZBP1), cyclic GMP-AMP synthase (cGAS), and stimulator of interferon genes (STING), which detect misplaced DNA and activate inflammatory responses. Using patient-derived heart cells and FA mouse models, the study will examine how mitochondrial dysfunction and DNA damage activate this pathway and determine whether it directly contributes to heart disease.
Dr. Feng will also evaluate a heart-targeted gene therapy designed to reduce ZBP1 activity in heart muscle cells. This work could uncover a previously unrecognized driver of cardiomyopathy and identify a new therapeutic strategy for protecting heart function in Friedreich’s ataxia.