A class of drugs used to treat erectile dysfunction could also treat blood-flow problems related to Duchenne muscular dystrophy--a bright spot in a disease field marked by repeated clinical setbacks.
In a small trial, boys with Duchenne given phosphodiesterase inhibitors--a class of drugs that includes sildenafil (Viagra) and tadalafil (Cialis)--had increased blood flow to muscles and less fatigue after exercising. Caused by a mutation in the dystrophin gene, the progressive, muscle-wasting disorder has no known cure.
Unlike the high-tech exon-skipping therapies that Sarepta ($SRPT) and Prosensa ($RNA) have been developing to go after the root cause of the disease, the new research indicates that the effect of the erectile dysfunction drugs would be limited to treating symptoms of Duchenne. But given the severity of the rare muscle-degrading disease, these boys and their parents are desperately searching for any new therapy that could help provide a benefit. This new study was conducted as patient groups angrily push the FDA to speed up new drug approvals, even as biotechs like Prosensa and PTC ($PTCT) regroup after past failures while Sarepta is trying to blaze a trail to an accelerated approval for its closely watched therapy.
The results from this new study are detailed in the May 7 online edition of the journal Neurology. In the study, 10 boys age 8 to 13 with Duchenne muscular dystrophy on corticosteroids were compared to 10 healthy boys of the same age. All of the boys in the study with Duchenne were able to walk, though some used a wheelchair or scooter. Blood flow in all of the participants' muscles was measured when they were at rest and when doing a handgrip exercise. The boys with Duchenne showed blood flow abnormalities even though they were taking corticosteroids, drugs that can slow muscle degeneration and help alleviate the effect on lung and heart function but are not well tolerated by many people with Duchenne.
Next, the boys with Duchenne were given either tadalafil or sildenafil and the tests were repeated. After two weeks, the boys received the other drug and the tests were repeated. The results showed that after taking either drug, the boys' blood flow response during exercise was the same as that of the boys who did not have the disease.
But the study authors acknowledge several limitations in their research.
"We do not know whether this improved blood flow regulation can be sustained with long-term use of the drug," Dr. Ronald Victor, assistant director of the Cedars-Sinai Heart Institute, said in a statement. "This proof-of-concept study also does not address the crucial question of whether restoring normal blood flow regulation will preserve muscle and slow disease progression."
Several Duchenne treatment approaches have been theorized, including increasing blood flow to muscles. In boys with Duchenne, dystrophin is missing from the muscle-fiber membrane. At the same time, another protein, known as nNOS, is also missing. The absence of nNOS results in an inability of the blood vessels supplying muscles to adequately dilate during exercise. Previous research has shown that when nNOS-deficient mice were treated with inhibitors used to treat erectile dysfunction, which dilates blood vessels, they were less fatigued after exercising.
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