Advancing novel mitochondrial therapies for FA cardiomyopathy: a pragmatic collaboration to move new therapies forward

In Friedreich’s ataxia, frataxin deficiency causes mitochondria dysregulation and impaired cellular energy production. Stealth BioTherapeutics has recently developed a series of new compounds that were designed to address dysregulated mitochondria in FA cardiomyopathy. These compounds have been developed to correct the impairments in bioenergetics of the cell and to prevent iron-mediated cell death (known as ferroptosis). Three compounds have been identified with the potential to mitigate mitochondrial dysfunction in FA cardiomyopathy: the first compound helps with improving energy production in mitochondria, the second prevents ferroptosis in cellular assays, and the third demonstrates potential “dual pharmacology” by improving both pathways. In this study, Dr. Kropp will test whether this series of compounds can ameliorate signs and disease biomarkers of cardiomyopathy in a mouse model of FA. She will also characterize the mechanism of these drugs by measuring their effect on energy production and ferroptosis in the FA mouse heart. These studies may provide new scientific insight as to whether inhibiting both pathways will be superior or equipotent to mechanistic approaches that inhibit either pathway alone. Successful completion of these studies will help to advance the development of a drug candidate for FA cardiomyopathy.