Treatment of Duchenne muscular dystrophy depends on time

Duchenne mainly affects men and is usually diagnosed at the age of 4. People born with Duchenne rarely live past the age of 20.

In 2017, researchers found that weekly doses of prednisone, a widely prescribed steroid, appeared to be more supportive of muscle weakness than daily doses while also reducing the effects. significant side effects from daily intake.

More than 2.5 million Americans use prednisone and similar drugs to control inflammation for conditions ranging from treating allergies to preventing organ transplant rejection.

Confirming a clear time-based effect on prednisone use in Duchenne patients would most likely improve outcomes for affected children, but it also raises questions about time of day. for other steroid use cases.

“Our internal clock system is quite complex,” says Quattrocelli.

In rats, the researchers found that a once-weekly dose of prednisone administered at the onset of the light period (around 7 a.m.) promoted muscle function.

The team observed that the treatment increased nutrient utilization and enhanced mitochondrial biogenesis in the muscle. It also increases endurance and improves muscle mass and strength. However, these reactions were lost when taking the drug during the dark ages.

With mice that are primarily nocturnal, their circadian clocks vary considerably from that of humans, so the specific time of day that is most beneficial to humans will be different from that of mice.

However, the researchers report that many of the time-based mechanisms involved in muscle cell activity are conserved between mice and humans, suggesting that timing will also be important in the treatment of these diseases. people with muscle disease.

If confirmed in future human studies, the findings suggest that the correct timing of dosing can maximize the benefit of the drug while avoiding the possible side effects of taking the drug. right time of day.

That could help improve treatment efficacy and possibly quality of life for a range of muscle conditions, from muscular dystrophy to aging to metabolic stress.

This study focused exclusively on prednisone and muscle tissue. The time-based efficacy of other synthetic glucocorticoids, such as dexamethasone and vamorolone (currently being tested for Duchenne muscular dystrophy (NCT03439670)) remains to be determined.

In addition to the different properties of drugs, different tissues have their own internal clocks. Therefore, more research will be needed to determine whether the effects of daytime and nighttime prednisone apply when treating conditions affecting other organ tissues.

Notably, most uses of prednisone involve controlling inflammation, often in immune conditions rather than muscle diseases. Studies on the time of day to treat immune conditions are just beginning.

Besides the obvious difference that rats are nocturnal animals while humans are mainly diurnal, we must consider many factors that will inevitably affect learning time in our population.

For example, humans have much more complex patterns of eating, working, playing, and sleeping than rats. All of these differences will need to be explored further to translate mouse-based learning to medical care for humans.

Source: Medindia

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