CHOP Researchers to Lead Department of Defense Project to Measure Mitochondrial Function and Better Detect Mitochondrial Disease

Researchers at Children’s Hospital of Philadelphia (CHOP) have received an $11.85 million Peer Reviewed Medical Research Program (PRMRP) Focused Program Award from the United States Department of Defense to develop and validate minimally invasive or noninvasive diagnostic techniques to quantify mitochondrial function in living people.

The award provides four years of funding for four projects, which will be led by Marni Falk, MD, Professor of Pediatrics and Executive Director of the Mitochondrial Medicine Program at CHOP. Over the course of these four projects, the team of nearly 50 researchers hopes to develop quantitative biomarkers and objective outcome measures that will improve detection of mitochondrial disease, assessment of disease severity and progression, and ultimately, the ability to monitor outcomes from therapeutic interventions in patients with primary mitochondrial disease as well as secondary mitochondrial disruption.

“It is deeply exciting to think about the potential impact this work may have on the future of mitochondrial disease diagnosis and care,” Falk said.

Mitochondria act as “batteries” by producing energy in the body’s cells. Low-functioning mitochondria can cause a wide range of health problems including fatigue, weakness, exercise intolerance, developmental disabilities, seizures, strokes  and serious problems with heart, liver or kidney function. As it is not possible to simply look at someone and judge how well their mitochondria are functioning, improved technological approaches to measure our body’s mitochondrial capacity rapidly and reliably are needed.

Overall, approximately 1 in every 4,300 individuals in the United States has a mitochondrial disease. Since the disease has the potential to present in a variety of ways, mitochondrial disease is often very difficult to diagnose or is misdiagnosed entirely. So far, more than 300 genes have been identified that are implicated in the development of mitochondrial disease. In addition, mitochondrial function fails in a host of other genetic and environmental disorders, including aging, neurodegenerative disease, traumatic brain injury, and acute illnesses including sepsis.

The four proposed projects include developing and validating a wireless, rechargeable nanosensor to measure oxygen levels in muscle after exercise; developing a “mitochondrial breathalyzer” to detect signs of energy deficiency in exhaled breath; measuring pupillary light reflex and remotely monitoring brain oxygen levels to determine autonomic nervous system dysfunction caused by mitochondrial failure; and determining effects of passive acceleration  – or movement without effort caused by an external force – on mitochondrial function. These technologies will be studied not only in patients with genetic-based primary mitochondrial diseases but also in individuals with secondary mitochondrial dysfunction from traumatic brain injury or while acutely ill in the intensive care unit.

Researchers from CHOP’s Mitochondrial Medicine Program will collaborate with a range of other CHOP experts across the Minds Matter Concussion Program, the Pediatric Intensive Care Unit (PICU), the Division of Infectious Diseases, and the Center for Mitochondrial and Epigenomic Medicine, as well as experts with the Singh Center for Nanotechnology at the University of Pennsylvania.

This work is supported by The Assistant Secretary of Defense for Health Affairs endorsed by the Department of Defense, in the amount of $11,855,637.00, through the Peer Reviewed Medical Research Program (PRMRP) under Award No. W81XWH-22-1-0590. Opinions, interpretations, conclusions and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.