The United Mitochondrial Disease Foundation (UMDF) is pleased to announce a new grant of $200,000 awarded to Suraiya Haroon, PhD, within Children’s Hospital of Philadelphia’s (CHOP) Mitochondrial Medicine Frontier Program (MMFP) research group through the generous support of The Cavan McGovern Family Fund, The Kamaria Satcher Fund for Kearn’s-Sayre Syndrome, and the CPEO/KSS Project Funds at UMDF to advance Single Large-Scale mtDNA Deletion (SLSMD) Syndrome Research Program.

“We are deeply grateful to partner with the UMDF and patient families to have this opportunity to take the next steps toward validating the preclinical safety and efficacy of therapeutic leads we have identified in SLSMD animal and cell models,” said Dr. Haroon, research assistant professor at CHOP MMFP and University of Pennsylvania Perelman School of Medicine.

The root cause of Kearns-Sayre Syndrome (KSS) and Pearson’s Syndrome (PS) is a problem with a part of the cells called mitochondrial DNA (mtDNA). Though KSS and PS have different symptoms, they both come from the same issue – a single, large-scale mtDNA deletion (SLSMD). It is unclear as to why some children get KSS or PS, even if they have the same SLSMD, but it is known that these diseases happen because of resulting problems with mitochondria function.

“When it comes to the families we serve, they only have one question,” said Philip Yeske, PhD, UMDF’s Science and Alliance Officer. “Will this get us one step closer to an FDA-approved treatment? And when it came to this project, we gave them an emphatic ‘yes.’ We’re extremely happy to have the world-class researchers at CHOP helping us chart the course for potential Single Large-Scale mtDNA Deletion Syndrome treatments.”

CHOP MMFP’s approach to finding treatments is to look for therapies that can fix the main cellular problem stemming from within the mitochondria, not just ease the symptoms. So far, they’ve identified several compounds that can make the mitochondria healthier in tests with SLSMD worm models. These compounds not only improve mitochondrial health but also seem to reduce the number of deleted mtDNA copies.

Excitingly, one compound has also shown to improve the worm model’s movement, indicating that the screening process can identify candidate therapies that not only help the mitochondria but also benefit the animals’ overall health. What’s even more promising is that they’ve tested these therapies after the animals already developed the disease. Researchers also plan to test other candidate therapies from additional small molecule compound screens, and validate lead findings by testing them on cell lines from KSS patients. CHOP has reached a critical stage for developing treatments, where the proposed study to validate treatment leads may ultimately be advanced to help not only KSS patients but potentially other individuals living with other types of mitochondrial disease.

“Advancing the pipeline of promising preclinical therapies to mitochondrial disease patients through precision clinical trials is a major focus and priority within the CHOP Mitochondrial Medicine Frontier Program”, said Dr. Marni Falk, professor and executive director at CHOP MMFP and University of Pennsylvania Perelman School of Medicine. “This important research will be carefully evaluated for the best lead(s) and timing to take them forward to directly study in patients.”