Cancer drug pulls surprising double duty to treat muscular dystrophy


Duchenne Muscular Dystrophy (DMD) is a debilitating genetic disorder that eventually leaves patients in a wheelchair. In a new study, researchers have found that an existing cancer drug shows promise in slowing the progress of DMD by changing the type of muscle fibers to be more resilient.

DMD occurs as the result of a gene mutation on an X chromosome, which reduces the production of a protein called dystrophin. Without it, muscle cells become fragile and easily damaged, leaving patients with progressively weaker muscle function. Eventually, the disease progresses to muscles involved in heart and lung function, resulting in a shortened life expectancy.

While there’s currently no cure, treatments to slow the progression of the disease are in development, such as drug combinations or boosting a related muscle-strengthening protein. Gene therapy could one day correct the disorder, with experiments on mice, dogs and pigs proving promising.

In the meantime, researchers at the University of British Columbia (UBC) have identified an existing drug that seems to slow the progression of DMD. The drug belongs to a group known as CSF1R inhibitors, which are already approved for use in humans to treat some forms of cancer by blocking a receptor that’s overexpressed in tumor cells.

Funnily enough, the researchers discovered the role of CSF1R inhibitors in DMD by accident. These drugs also work to deplete microglia, the resident macrophages in the central nervous system, which has been explored as a way to “reset” the population of these cells. In this case, the UBC team was investigating the role of these macrophages on muscle regeneration. But when they depleted the macrophages of mice, they found that the animals’ muscle fibers surprisingly changed into a type that’s more resistant to the damage induced by muscular dystrophy.

“Many people will have heard that there are different types of muscle fibers, including fast-twitch and slow-twitch muscles,” said Fabio Rossi, senior author of the study. “By administering this drug, we observed that the muscle fibers actually started to transition to a slower-twitch type that is more resistant to damage caused by muscle contractions.”

To investigate further, the researchers tested the drug on mice with DMD, and found that within a few months treated mice had a higher percentage of damage-resistant muscle fibers compared to control mice. They were able to perform physical activities like running on a treadmill better too, with the team describing the improvement to their muscle resiliency as “profound.”

While more work is needed before this treatment could be used in humans, the fact that CSF1R inhibitors are already in use in humans for other illnesses should speed up development.

“Developing a new drug can be a long process,” says Rossi. “But with the safety profile for this drug already being proven in human studies, it could mean we’re on a fast track to a new treatment for muscular dystrophy.”

The research was published in the journal Science Translational Medicine.

New Atlas, 3 July 2022