‘Weekend pill’ employed for muscular dystrophy

A drug used to treat erectile dysfunction may prevent functional muscle ischemia in patients with Becker muscular dystrophy, a small randomized trial shows.

"This is not a cure, but it could be the first step toward identifying potential treatments for Becker muscular dystrophy," said lead researcher Ronald Victor (Cedars-Sinai Medical Center, Los Angeles, California) in a press statement.

In this indication, the drug, tadalafil, works by boosting signaling of nitric oxide, thereby preventing vasoconstriction and allowing increased perfusion to cope with the demands of exercise. Victor and team previously showed that this process, known as functional sympatholysis, is impaired in patients with muscular dystrophy. This leads to exercise-induced muscle ischemia, which may accelerate damage in muscles already suffering from dystrophin deficiency.

The seven healthy controls involved in the trial exhibited functional sympatholysis; the decrease in forearm muscle oxygenation in response to lower-body negative pressure was attenuated by about 60% if they performed a handgrip exercise. By contrast, just one of the 10 patients with Becker muscular dystrophy had this reaction.

When all the patients were re-assessed at least 3 hours after taking a single capsule of tadalafil 20 mg, the handgrip exercise caused an average 52% attenuation in the decrease in forearm muscle oxygenation. The average reductions in oxygenation were 17% at rest and 9% during handgrip, with all but one patient benefiting from the drug.

No such effect was seen after the patients took a placebo capsule, with average 18% and 17% reductions in oxygenation seen at rest and during handgrip, respectively.

Patients and researchers were unaware of which pill had been taken, and there was a 2-week washout period between assessments, the team notes in Science Translational Medicine.

The patient with evidence of functional sympatholysis without tadalafil treatment had deletions of exons 45-48 of the dystrophin gene. This, the researchers found, resulted in a truncated form of dystrophin that allowed some increase in nitric oxide signaling in response to muscle use. The patient who did not benefit from tadalafil had deletions of exons 3-7.

"Providing adequate oxygenation to muscles already weakened by abnormal dystrophin may be a strategy to slow the course of the disease," remarked Victor.

He added: "Since no new drug development would be needed, repurposing it for muscular dystrophy could quickly transform clinical practice."

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