Mitochondrial Medicine

Mitochondria function as the biological batteries that produce energy within our body's cells. Depending on which cells have low-functioning mitochondria, mitochondrial disease can cause a wide range of health problems, including fatigue, weakness, exercise intolerance, developmental disabilities, seizures, strokes, vision or hearing loss, growth and feeding difficulties, hormone imbalances, as well as serious problems with heart, liver, or kidney function. On average, people with mitochondrial disease have 16 major medical problems. Researchers are continually working to identify new types of mitochondrial disease, which are now known to result from pathogenic variants in more than 350 different genes, and their various crossroads with other conditions.

This Frontier program seeks to characterize exactly how mitochondrial disease affects the body; develop improved diagnostic genetic, biochemical, tissue, and imaging testing; and lead the way toward precision therapies to treat and manage mitochondrial disease. Efforts under way in the Center for Mitochondrial and Epigenomic Medicine and across many collaborating specialties at CHOP converge to establish a deeper understanding of how energy production in mitochondria relates to a wide range of diseases and conditions.

Here are some highlights of Mitochondrial Medicine's research efforts:

• CHOP researchers continue to work on developing and launching new pharmaceutical-sponsored as well as investigator-initiated clinical trials in mitochondrial disease, while learning from patients what best motivates or hinders their clinical trial participation.
• Researchers from CHOP have continued to discover and understand novel gene causes for Leigh syndrome, and they have led national and international efforts to expertly curate the more than 90 different genes and reported pathogenic variants.
• CHOP researchers continue to investigate a mystery surrounding mitochondrial proteins and cellular stress responses.
• Successful partnerships with mitochondrial disease patients and families have been established to support precision therapeutic development, working with translational research model animals and cells from patients with primary mitochondrial diseases.
• More than two dozen clinical diagnostic tests at CHOP are being developed to better diagnose and monitor mitochondrial disease, including needle muscle biopsies and highly sensitive mitochondrial DNA genome sequencing and deletion quantitation.
• Marni Falk, MD, Executive Director of the Mitochondrial Medicine Program, weighed in on ethical considerations for new reproductive technologies to prevent inheritance of mitochondrial diseases, and Dr. Falk participates in national and international efforts to speed the development of new therapies for these severe diseases.

The Mitochondria Medicine Program received Frontier status in Fiscal Year 2018.