A Potential Treatment for Muscular Dystrophy
The School of Biomedical Engineering at the University of British Columbia (UBC) revealed that an existing cancer treatment could be used to treat muscular dystrophy.
The drug, known as a colony-stimulating factor 1 receptor (CSF1R) inhibitor, was discovered to significantly halt the progression of Duchenne muscular dystrophy in mice by boosting the resilience of muscle fibers.
The results were recently published in the journal Science Translational Medicine.
“This is a class of drug that is already being used in clinical trials to treat rare forms of cancer,” says Dr. Farshad Babaeijandaghi, a postdoctoral fellow at UBC and first author on the study. “To find that it could potentially serve a double purpose as a treatment for muscular dystrophy is incredibly exciting. It shows a lot of promise, and with further testing, could help extend and improve quality of life for patients.”
Duchenne muscular dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle weakening and degeneration caused by abnormalities in the protein dystrophin, which helps maintain muscle cells. It is the most prevalent congenital condition in Canada, affecting about one in every 3,500 boys and, in rare occasions, females.
DMD symptoms often develop in early infancy, with patients experiencing progressive muscular function loss as they mature. As the condition develops, many people must depend on mobility aids such as a wheelchair, and the disease eventually affects heart and lung function. While advances in heart and respiratory treatment have enhanced life expectancy in recent decades, there is no cure at the moment.
“Muscular dystrophy is a devastating disease that impacts children at a young age. While this is not a cure, it could significantly delay disease progression, helping people stay mobile and out of wheelchairs for longer,” says the study’s senior author Dr. Fabio Rossi, a professor at UBC’s school of biomedical engineering and department of medical genetics. “It could be used in conjunction with other treatments and emerging gene therapy approaches aimed at the genetic defect.”
The findings caught the researchers by surprise while they were initially studying the role of resident macrophages — a type of white blood cell — in muscle regeneration.
During experimentation in mice, they found that CSF1R inhibitors, which deplete resident macrophages, had the unexpected effect of making muscle fibers more resistant to the type of contraction-induced tissue damage that is characteristic of muscular dystrophy. The drug had the effect of changing the type of muscle fibers in the animal’s body from damage-sensitive type IIB fibers to damage-resistant type IIA/IIX fibers.
“Many people will have heard that there are different types of muscle fibers, including fast-twitch and slow-twitch muscles. 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,” says Dr. Rossi.
After making the discovery the researchers tested the drug in mice with DMD. Within a few months of treatment, they began to see successful results. The mice that underwent treatment showed higher frequencies of damage-resistant muscle fibers and were able to perform physical tasks, like moderate running on a treadmill, with less muscle damage than their untreated counterparts.
“The results were actually quite dramatic. The improvement in muscle resiliency was profound,” says Dr. Babaeijandaghi.
The researchers say that further studies are needed to identify if CSF1R is effective at treating DMD in humans. Considering that several short-term clinical studies have already shown that this class of drug is safe for use in people, they’re hopeful that it could mean a patient-ready treatment is on the horizon.
“Developing a new drug can be a long process,” says Dr. 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.”
Reference: “Metabolic reprogramming of skeletal muscle by resident macrophages points to CSF1R inhibitors as muscular dystrophy therapeutics” by Farshad Babaeijandaghi, Ryan Cheng, Nasim Kajabadi, Hesham Soliman, Chih-Kai Chang, Josh Smandych, Lin Wei Tung, Reece Long, Amirhossein Ghassemi and Fabio M. V. Rossi, 29 June 2022, Science Translational Medicine.
The study was funded by the Canadian Institutes of Health Research.