Cyclosporine A in Ullrich Congenital Muscular Dystrophy : Long-Term Results

• Published in: Oxidative medicine and cellular longevity Vol. 2011; no. 2011; pp. 1 - 10
• Main Authors: Franchella, Andrea, Gualandi, Francesca, Bertini, Enrico, Maraldi, Nadir Mario, Ferlini, Alessandra, Bonaldo, Paolo, Bernardi, Paolo, Merlini, Luciano, Michelini, Maria Elena, Grumati, Paolo, Angelin, Alessia, Sabatelli, Patrizia, Armaroli, Annarita, Gnudi, Saverio
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2011; Hindawi Publishing Corporation
• Subjects: Apoptosis - drug effects; Child; Child, Preschool; Collagen Type VI - metabolism; Cyclosporine - pharmacology; Cyclosporine - therapeutic use; Enzyme Inhibitors - pharmacology; Enzyme Inhibitors - therapeutic use; Female; Humans; Male; Membrane Potential, Mitochondrial - drug effects; Muscle Strength - drug effects; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Muscular Dystrophies - drug therapy; Muscular Dystrophies - genetics; Mutation; Regeneration - drug effects; Sclerosis - drug therapy; Sclerosis - genetics
• ISSN: 1942-0900; 1942-0994
• DOI: 10.1155/2011/139194

Six individuals with Ullrich congenital muscular dystrophy (UCMD) and mutations in the genes-encoding collagen VI, aging 5–9, received 3–5 mg/kg of cyclosporine A (CsA) daily for 1 to 3.2 years. The primary outcome measure was the muscle strength evaluated with a myometer and expressed as megalimbs. The megalimbs score showed significant improvement (P=0.01) in 5 of the 6 patients. Motor function did not change. Respiratory function deteriorated in all. CsA treatment corrected mitochondrial dysfunction, increased muscle regeneration, and decreased the number of apoptotic nuclei. Results from this study demonstrate that long-term treatment with CsA ameliorates performance in the limbs, but not in the respiratory muscles of UCMD patients, and that it is well tolerated. These results suggest considering a trial of CsA or nonimmunosuppressive cyclosporins, that retains the PTP-desensitizing properties of CsA, as early as possible in UCMD patients when diaphragm is less compromised.