Countdown Awards Research Grant to Advance Mitochondrial Transplantation in Duchenne Muscular Dystrophy 

James D. McCully, PhD, D.Sc (Hon) | Associate Professor of Surgery at Harvard Medical School and the Department of Cardiac Surgery at Boston Children’s Hospital

Countdown Funding Pillars: Advanced Therapeutics & Frontier Innovation; Chronic Disease & Aging; Primary Mitochondrial & Rare Genetic Disease

GLP-1 medications have changed the conversation around weight loss for millions of people, but they’ve also surfaced a less-discussed side effect: muscle loss.

Research shows that lean muscle mass can account for roughly 25 to 40% of total weight loss on GLP-1 therapies, a meaningfully higher share than typically seen with diet alone. As adoption of these drugs continues to climb, preserving muscle — and the cellular energy that powers it — is becoming a bigger question in medicine, not a smaller one. 

What if muscle didn’t have to fail as we age, or as disease progresses — because we could restore its energy supply directly? 

That’s the question at the center of Countdown’s newest research grant, awarded to Dr. James McCully at Boston Children’s Hospital. 

The Research

Muscle degeneration shows up everywhere; in aging, in chronic disease, with the increasing use of GLP-1 medications, and in genetic conditions like Duchenne muscular dystrophy (DMD). It looks different on the surface depending on the cause, but underneath, the story is the same: muscle weakens, and repair slows or stops entirely — muscle gets worse, not better — because the cells powering that muscle are running out of energy. Despite how central this is, there is currently no treatment that directly restores energy in struggling muscle cells. 

Dr. McCully’s research takes a direct approach: mitochondrial transplantation. The strategy involves isolating healthy, functioning mitochondria and delivering them directly into compromised tissue, where they integrate into the existing cells and restore the energy production that tissue needs to function and repair itself. His team, including lead investigator Aybüke Çelik PhD, will study this approach in a genetic model of DMD, testing both single and repeated delivery alongside a new hydrogel-based system designed to help the transplanted mitochondria stay in place longer and work more effectively, with the goal of moving this closer to real clinical use. 

Why Duchenne Muscular Dystrophy? 

Duchenne muscular dystrophy is one of the most severe forms of muscular dystrophy, caused by a genetic mutation that leaves muscle cells unable to produce a protein needed to keep muscle fibers intact. At the root of that breakdown is mitochondrial dysfunction — the muscle’s energy factories failing — which drives the chronic inflammation, oxidative stress, and impaired cell signaling that push the disease forward. Over time, muscle breaks down faster than the body can repair it, leading to progressive weakness, loss of mobility, and, eventually, heart and respiratory failure. It’s rare, it’s aggressive, and it’s almost entirely defined by a failure of muscle cells to sustain themselves, which is exactly why it makes such a powerful test case. If mitochondrial transplantation can measurably improve muscle survival and function in a disease this severe, it builds the clinical and scientific case for using the same approach in conditions where muscle loss is a symptom rather than the root cause. 

Decades in the Making 

This isn’t a new idea for Dr. McCully, it’s the next chapter of one he began over two decades ago. In 2014, he developed an NIH-funded technique that isolated healthy mitochondria and transplanted them into damaged tissue, first proving it in mice and pigs. Then came the moment that changed everything: an infant at Boston Children’s Hospital with a life-threatening heart defect, too sick to survive surgery alone. With no other options left, Dr. McCully and his surgical colleagues extracted healthy mitochondria from the baby’s own abdominal muscle tissue during the operation and reinjected them directly into her heart. Within minutes, the tissue changed color and began beating again. She recovered fully and today is a thriving, active 12-year-old. 

That case became the first in a new field and one built on the patient’s own mitochondria. This next phase takes the science further: rather than harvesting from the patient’s own tissue, the DMD research will draw on an outside mitochondrial source, a shift that could make the therapy far easier to produce and deliver at scale. What started as a last-resort intervention for infant heart patients has since expanded into research on the brain, kidney, lung, eyes, and now — with Countdown’s support — muscle. 

One Mechanism. Every Disease. 

Because mitochondrial dysfunction is the shared root cause across nearly every one of these conditions, this approach doesn’t depend on a specific genetic mutation which means it will eventually help patients who don’t qualify for gene-specific treatments and can work alongside existing therapies rather than replacing them. The same underlying failure — muscle running out of the energy it needs to function and repair itself — shows up in cardiomyopathies, age-related sarcopenia (the natural, progressive loss of muscle mass and strength that typically begins in your 30s and accelerates after 60), cachexia (severe, unintentional muscle and weight loss driven by systemic inflammation from diseases like cancer, COPD, or heart failure), and simple atrophy from inactivity or bed rest. It shows up in autoimmune disease. It even shows up in elite athletes, whose bodies absorb repeated physical stress that mitochondrial transplantation could one day help repair. This isn’t a niche mechanism, it’s foundational to nearly every form of muscle decline the body can experience. 

Why Countdown Funded This 

This is exactly the kind of science Countdown exists to accelerate: bold, high-risk research with the potential to preserve muscle, restore function, and change lives. We believe the greatest breakthroughs are the ones that move beyond the laboratory and into the lives of patients and families, and that kind of progress requires partners willing to invest in innovative science at its earliest stages. This research was made possible in part through the support of PS Cares, the philanthropic arm of PS Reserve, whose team shares Countdown’s belief that restoring energy and function at the cellular level is where the future of health is headed. 

It’s also a clear example of how Countdown funds. Every project we back, across all six of our research pillars, shares the same organizing principle: mitochondria are the engine of human health. We don’t fund science in isolation; we fund it in orchestration. Dr. McCully’s research doesn’t just stand on its own; it connects to Countdown’s broader portfolio in diagnostics, treatment, and ongoing measurement, building toward a future where mitochondrial health can be identified early, treated directly, and tracked over time — the same connected system his own path from an infant heart patient to a DMD model already demonstrates. 

Fund the Future

Muscle degeneration is one of the most visible signs of a much deeper issue: the breakdown of cellular energy. Dr. McCully’s research is a step toward changing that, not just for one disease, but for the biology every form of muscle decline shares. This is what it means to fund mitochondrial science as a connected system rather than a collection of isolated conditions.

To learn more about Countdown’s mission, get involved, or help fund bold, high-risk, high-reward mitochondrial research, please explore how to get involved — which includes our recently introduced membership program, Countdown Insiders ($21/mo or $252/year). In addition to helping fund research like Dr. McCully’s, Insiders provides a front row seat to mitochondrial health, curated conversations, member experiences, and partner perks. Together, we can accelerate the future of human health.

Read the full press release here and learn more about Countdown Insiders here.