Using glucocorticoid steroids once a week instead of once a day to slow the progression of muscular dystrophy (MD) could prevent downsides of the treatment, including accelerated muscle wasting, a study reports.
Researchers at the Feinberg School of Medicine at Northwestern University discovered that mice with Duchenne muscular dystrophy fared better taking steroids once a week instead of daily. They want to see if the same is true in humans.
The study, “Intermittent glucocorticoid steroid dosing enhances muscle repair without eliciting muscle atrophy,” was published in the Journal of Clinical Investigation.
Glucocorticoid steroids prolong the time until muscular dystrophy patients lose their ability to walk. But they have the paradoxical side effect of accelerating muscle breakdown when used long-term.
Although once-a-day dosing is standard in long-term steroid use, children are sometimes treated once a week to reduce the therapy’s effect on their behavior, researchers noted.
To test the idea that a once-a-week dose could work with adults, the team treated half of the Duchenne MD mice in their experiment daily and half weekly. They also performed the experiments in mice with acute muscle injury.
Mice treated daily ran for a shorter time on a treadmill than controls. In contrast, those that received weekly doses ran longer. Muscle fiber types and sizes were different in the daily- and weekly-dosed animals, the researchers discovered.
Tests of muscle mass and force showed a similar picture: Mice on weekly doses benefitted more from the treatment.
Interestingly, researchers found no differences in heart muscle measurements between the daily- and weekly-dosed groups. The mice on both regimens performed equally well.
To understand how differences in dosing interval translated to differences in treatment effectiveness, the research team studied molecular changes in the mice’s muscles.
They noted that both daily and weekly dosing activated molecular pathways that improved muscle repair. But daily administration also triggered events linked to accelerated muscle breakdown.
Weekly dosing actually reduced activity in some of the cell signaling pathways linked to muscle wasting.
The researchers also found no differences in the glucocorticoids prednisone and deflazacort’s ability to foster muscle repair.
In a press release, the researchers said studies are needed on whether the findings will apply to humans.