Could Utrophin Rescue the Myocardium of Patients with Dystrophin Gene Mutations?

Abstract

The spontaneous up-regulation of utrophin, observed in dystrophin-deficient skeletal muscle fibers, may decrease the susceptibility of such fibers to necrosis. It has been reported that the utrophin-rescued double-mutant mdx mouse always develops a lethal cardiomyopathy. We report two patients with severe dilated cardiomyopathy due to dystrophin gene mutations: the first was a manifesting Duchenne muscular dystrophy carrier and the second a patient affected with moderate Becker muscular dystrophy. We studied their explanted heart specimen and/or endoÍmyocardial biopsies by immunohistochemistry and Western blot for both dystrophin and utrophin. Utrophin was found to be over-expressed in these specimens. Our results suggest that in these patients the up-regulation of utrophin in dystrophin-deficient cardiomyocytes was unable to prevent the development of life-threatening myocardial dysfunction. These findings seem to dampen the enthusiasm raised by the prospect of DMD treatment by utrophin rescue in skeletal muscle fibers, as the myocardium would still remain severely affected.