Effect of Modulating the nNOS System on Cardiac, Muscular and Cognitive Function in Becker Muscular Dystrophy Patients
Status:
Completed
Trial end date:
2013-04-01
Target enrollment:
Participant gender:
Summary
This study is done to evaluate whether treatment with the drug sildenafil (Revatio®) can
improve muscular, cardiac, cerebrovascular or cognitive function in patients with Beckers
muscular dystrophy when compared to placebo (inactive medication). The study is based on the
recent findings of an improved cardiac function in a mouse model of muscular dystrophy (Adamo
et al 2010) and the previous findings of changed cognitive function in people with Becker
dystrophy.
In muscular dystrophy, the cellular protein, dystrophin is affected. During normal
conditions, the enzyme neuronal nitric oxide synthase (nNOS), which produce nitric oxide
(NO), is attached to dystrophin. NO is important in normal vascular function in each of
muscle, heart and brain by stimulating production of cyclic GMP. However, in muscular
dystrophy with dystrophin deficiency, nNOS do not have the normal cellular anchor, resulting
in decreased NO levels and subsequent reduced cyclic GMP production. Sildenafil inhibits
degradation of cGMP thus prolonging and increasing a cGMP response. Such effects are the
basis for use of sildenafil in pulmonary hypertension and erectile dysfunction. Current
hypothesis: Sildenafil restores the cyclic GMP function affected in muscular dystrophy wit
nNOS deficiency resulting in improved muscle, cardiac, cerebrovascular and cognitive
function.