MDA-led project to map how human muscles repair themselves
Researchers aim to accelerate development of muscle-regeneration therapies
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A research collaboration led by the Muscular Dystrophy Association (MDA) aims to create a molecular map of human muscle regeneration, a project that could accelerate the development of muscle repair-based therapies for people with muscular dystrophy (MD).
Abigail Mackey, PhD, a professor of muscle physiology and regeneration at Copenhagen University Hospital, will lead the project, titled “Regenerating healthy human skeletal muscle at single nucleus resolution.” The goal is to understand “normal” human muscle repair at a highly detailed molecular level and to identify altered processes in neuromuscular diseases, the MDA said.
“Human muscle has an extraordinary capacity to heal, yet we’ve never been able to observe that process with the cellular detail this study will provide,” Mackey said in an MDA press release. “By capturing regeneration at single-nucleus resolution — and by contrasting healthy and disease-affected muscle — we aim to reveal the precise molecular steps where the process succeeds or breaks down.”
MD is a group of genetic muscle disorders characterized by progressive muscle weakness and wasting. The muscles that control voluntary movements are typically the most affected, although other muscle groups, such as those involved in breathing and heart function, may also be affected.
Drugs approved for MD mainly work to prevent or slow muscle loss, but they don’t promote muscle repair, making them less likely to benefit patients with advanced muscle loss.
Focus on human muscles
Most muscle-regeneration studies have focused on animal models. The basic mechanisms of muscle regeneration in humans have been poorly investigated, despite key differences in the course of tissue repair.
The researchers also noted that most strategies aimed at boosting muscle regeneration have focused on muscle stem cells, but other cell types and the mesh-like matrix surrounding cells also play key roles.
One major hurdle identified at the MDA Muscle Regeneration Summit, held in 2024 in Quebec, was a lack of understanding of how muscle regeneration occurs and which cells and processes control it. The conference “underscored the need to understand muscle repair not just at the stem cell level, but across all cell types and the extracellular matrix that together orchestrate regeneration,” said Angela Lek, PhD, chief research officer at MDA.
“The summit clarified a need the community has expressed for years — to build a true, human-based picture of how muscle regeneration works,” Lek said. “This project is a direct outcome of that meeting: collaborative, ambitious, and designed to accelerate therapies that target muscle regeneration and repair across multiple neuromuscular conditions.”
The researchers will use state-of-the-art technologies to detail, at the single-nucleus level, the molecular pathways involved in human muscle repair. Some muscle cells contain hundreds to thousands of nuclei (the cellular compartment that houses DNA), and single-nucleus analysis is used to determine gene activity in each of those nuclei.
After studying how human muscle regenerates in healthy people, the researchers will compare their data with muscle samples from people with Duchenne muscular dystrophy, facioscapulohumeral muscular dystrophy, and limb-girdle muscular dystrophy 2L to determine how muscle regeneration is altered in neuromuscular diseases.
Organizations including the Parent Project Muscular Dystrophy (PPMD), the LGMD2L Foundation, and the FSHD Society are also involved in the project.
“For the Duchenne community, supporting regenerative research is essential to driving therapies that can meaningfully strengthen or restore muscle,” said Eric Camino, PhD, vice president of research and clinical innovation at PPMD.
For Hal Tily, vice president of research at LGMD2L Foundation, “understanding why muscle breaks down and why repair fails is central to developing future treatments” for people living with LGMD2L. “This project brings us meaningfully closer to that understanding.”
