Bethlem Myopathy and Ullrich Congenital Muscular Dystrophy (UCMD) are muscle-wasting diseases caused by deficiencies in collagen VI, a component of connective tissue. Patients are usually diagnosed at birth and suffer from muscle weakness that worsens over time. UCMD patients often also suffer respiratory failure, which is complicated by lung infections. Although the drug cyclosporin A (CsA) offers some benefit for these patients, its long-term use may be undesirable because it interacts with calcineurin, an important immunoregulatory protein, thus exposing patients to potentially harmful immunosuppression. In this study, Tania Tiepolo, of the University of Padova in Italy, and colleagues assessed the effects of a new drug called Debio 025 in a mouse model of collagen VI muscular dystrophies. After just five days treatment with Debio 025, both intraperitoneal and oral administration prevented mitochondrial dysfunction and normalized the apoptotic rates and ultrastructural lesions in the treated mice. Debio 025 showed great potential for slowing the progression of the muscle wasting disease. More importantly, unlike cyclosporine A, Debio 025 did not display affinity for calcineurin and therefore lacks immunosuppressive activity, making it suitable for long-term use. This implies that Debio 025 may provide a safer alternative to CsA in muscular dystrophy. These findings provide an important proof of principle that collagen VI muscular dystrophies can be treated with Debio 025 and represents an essential step towards an effective therapy for Ullrich Congenital Muscular Dystrophy and Bethlem Myopathy because Debio 025 does not expose patients to the potentially harmful effects of immunosuppression.

Références : Br J Pharmacol. 2009 Jun 10. [Epub ahead of print]