Could utrophin rescue the myocardium of patients with dystrophin gene mutations?

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 mds mouse always develops a lethal cardiomyopathy. We report two patients with severe dilated cardiomyopathy due to dystrophin gene mutations: the first w as a manifesting Duchenne muscular dystrophy carrier and the second a patie nt affected with moderate Becker muscular dystrophy. We studied their expla nted heart specimen and/or endomyocardial 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 patie nts the up-regulation of utrophin in dystrophin-deficient cardiomyocytes wa s unable to prevent the development of life-threatening myocardial dysfunct ion. These findings seem to dampen the enthusiasm raised by the prospect of DMD treatment by utrophin rescue in skeletal muscle fibers, as the myocard ium would still remain severely affected, (C) 1999 Academic Press.