Loss of laminin-α2 may lead to muscular dystrophy

For more than two decades, researchers have been investigating a severe form of muscular dystrophy in which muscles progressively degenerate. The research team has now discovered that the muscles’ ability to regenerate is also impaired. Future therapies should therefore aim not only to strengthen muscles but also to promote their regeneration.

Roughly eight in every million children are born with a particularly severe form of muscle weakness known as LAMA2-related muscular dystrophy. In Switzerland, 18 cases are currently known. This rare hereditary disease is still incurable. The muscles of affected children gradually become weaker, including the respiratory musculature. In many cases, the children do not reach adulthood.

The disease is caused by a genetic defect that prevents cells in the human body from producing the protein laminin-α2. In skeletal muscle, this protein is part of the extracellular matrix that surrounds muscle fibers and helps to maintain their structural integrity. Without laminin-α2, even normal muscle use causes damage, leading to progressive muscle loss.

The researchers have now discovered that laminin-α2 also has an important influence on muscle stem cells, which are essential to generate new muscle fibers after muscle injury. Their study has been published in Nature Communications.

Muscle stem cells reside dormant in specialized niches between muscle fibers. When muscle injuries occur, they become activated, start dividing, and differentiate to form new muscle fibers. In healthy muscle, these stem cells also produce laminin-α2 themselves and release it into their environment to support their proliferation.

“We were surprised to see that muscle stem cells actually rely on their own laminin-α2 to efficiently generate new muscle fibers,” says the study’s first author. “In diseased mice lacking laminin-α2, muscle stem cells proliferate much more slowly and muscle repair after injury is severely impaired.” In other words, the muscles degenerate faster than they can regenerate.

In experiments with human cells, the researchers confirmed these findings. “Human muscle stem cells also produce laminin-α2, and preventing them from doing so impairs their proliferation”, explains the author. Laminin-α2 produced by stem cells therefore plays a crucial role in regenerating damaged muscles.

“So far, laminin-α2 has been recognized primarily for its role in stabilizing muscle fibers,” says the author. “Our findings now demonstrate that this protein is also crucial for the regenerative capacity of muscle stem cells. Based on our data, the best strategy for future therapies to mitigate symptoms of muscular dystrophy and slow disease progression will be to target both muscle fibers and muscle stem cells.”

https://www.nature.com/articles/s41467-025-65703-1

https://sciencemission.com/aminin--%CE%B12-drives-muscle-stem-cell-dysfunction