Combo Therapy Restores Muscle Function in Mice With Duchenne Muscular Dystrophy

A combination of two treatments significantly approved muscle function in mice with Duchenne muscular dystrophy (DMD), a study shows.

Since both treatments are already approved, the findings “may open up new therapeutic avenues for Duchenne muscular dystrophy and possibly other neuromuscular diseases,” the researchers said.

The study, “Osteoprotegerin and β2-agonists Mitigate Muscular Dystrophy in Slow- and Fast-Twitch Skeletal Muscles,” was published in The American Journal of Pathology.

Earlier the team found that a bone and skeletal-muscle protector, osteoprotegerin immunoglobulin fragment complex (OPG-Fc), restored the function of the mice’s fast-twitch extensor digitorum longus (EDL) muscles.

This time researchers wanted to know if OPG-Fc and a new-generation β2-agonist would work together to improve both slow- and fast-twitch muscle function. Although OPG-Fc improves such functioning,  side effects in bone and cardiac tissue have limited its use.

Slow-twitch soleus (SOL) muscles govern muscular endurance. Fast-twitch muscles are used in rapid movements, such as jumping.

The mice were divided into four groups. One group was injected only with OPG-Fc, another only with the new-generation β2-agonist formoterol, and a third group with a combination of the therapies. The fourth cohort was a control group.

Formoterol was administered in both low and high doses.

Researchers found that OPG-Fc combined with a low dose of formoterol restored slow-twitch muscle function. They also discovered that OPG alone was far superior than any dose of formoterol in restoring fast-twitch muscles.

In addition, they learned that OPG-Fc restored a key protein receptor’s ability to regulate muscle mass.

Another finding was that, when combined with OPG-Fc, less formoterol needs to be used on muscle twitching. That will reduce the side effects that affect bone and heart function.

The research team still needs to discover why OPG-Fc and formoterol work so well together to restore muscle function.

“Because osteoporosis and muscle atrophy/degeneration worsen in tandem during neuromuscular diseases, and because OPG-Fc has a beneficial effect on skeletal muscle and bone functions, we have high hopes that this combined treatment may open the way for new treatments for DMD patients,” the researchers concluded.