A DRUG INHIBITS THE MITOCHONDRIAL PROTEASE INDUCING CALMITINE DEFICIENCY IN SKELETAL-MUSCLE OF PATIENTS WITH DUCHENNES MUSCULAR-DYSTROPHY AND DY DY DYSTROPHIC MICE/

This study demonstrates that the cause of calmitine deficiency in dy/d y dystrophic mice and patients with Duchenne's muscular dystrophy (DMD ) is the same; i.e., the absence of an inhibitor of calmitine-specific mitochondrial protease. This inhibitor, which is present in control m ice and control subjects, prevented degradation of the protein. It is also shown that a drug (IP96) was capable in vitro of inhibiting calmi tine-specific mitochondrial protease from muscle of DMD patients and d y/dy mice. This drug was also active in vivo in an experimental model of myopathy created in the normal mouse by a single injection of chlor promazine, a myotoxic drug, which induced temporary calmitine degradat ion. Thus, it seems quite likely that IP96 prevents calmitine degradat ion by inhibiting the specific protease. (C) 1997 Academic Press.