Hansell Stedman, MD, a professor of Surgery at Penn Medicine and a competitive cross-country skier, has combined his expertise in athletics with decades of research on Duchenne muscular dystrophy (DMD). DMD is a genetic disorder that leads to progressive muscle degeneration and was responsible for the deaths of Stedman's two brothers.
Stedman’s understanding of muscle function comes from both personal experience as an athlete and his scientific background. As he trains for events such as the Masters World Cup and Winter World Masters Games, he applies knowledge gained from years of studying muscle fibers and metabolic pathways. “There's a dividend here,” said Stedman. “Because it’ll allow me to compete in a muscle physiology-driven sport by understanding how to focus on what matters most in training and recovery.”
Stedman's laboratory at the Pennsylvania Muscle Institute (PMI) within the Perelman School of Medicine brings together researchers with backgrounds in both science and athletics. The team includes an elite rower who uses her athletic training to design experiments, as well as a Penn senior with DMD who participates as both researcher and therapy recipient.
Research into DMD took a major step forward when scientists identified the gene responsible for producing dystrophin, a protein that stabilizes muscle cells. In people with DMD, mutations disrupt dystrophin production, making muscle cells more susceptible to damage.
Gene therapy has emerged as an important approach for treating genetic disorders like DMD. In the 1990s, Stedman's research progressed toward clinical trials before safety concerns slowed development across the field following an unrelated participant death in 1999. Since then, gene therapies have gradually advanced through regulatory approval processes.
“One of the bitter lessons is that the difference between a curative experience with gene therapy and a lethal complication is usually driven by the immune response,” said Stedman. “We are now building on generous support from the PMI, the National Institutes of Health, and a Penn startup biotech company StrongHolt Therapeutics to address these issues head on.”
Recent studies led by members of Stedman's lab tested exercise regimens paired with utrophin gene therapy in mice models of DMD. The results showed that treated mice ran faster for longer periods and had improved protection against heart damage—a significant step toward eventual clinical trials. Stedman co-founded StrongHolt Therapeutics to help manage manufacturing and regulatory steps needed for these trials, which could begin within two years at Children’s Hospital of Philadelphia.
For patients like Gambhir—a Penn senior living with DMD—gene therapy remains both promising and uncertain due to immune system challenges resulting from previous treatments. Still, Gambhir expressed optimism: “I’m particularly interested in getting rid of DMD so no one else has to deal with what I’ve gone through,” he said.
Another researcher in Stedman’s group drew parallels between athletic endurance training and scientific persistence: “It’s like training,” Kasden said. “You just have to continue to show up.”
