Cyclosporine A in Ullrich congenital muscular dystrophy: long-term results.
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.
Section of Medical Genetics, Department of Experimental and Diagnostic Medicine, University of Ferrara, 44121 Ferrara, Italy. luciano.merlini@unife.it
Luciano
L
Merlini
Patrizia
P
Sabatelli
Annarita
A
Armaroli
Saverio
S
Gnudi
Alessia
A
Angelin
Paolo
P
Grumati
Maria Elena
ME
Michelini
Andrea
A
Franchella
Francesca
F
Gualandi
Enrico
E
Bertini
Nadir Mario
NM
Maraldi
Alessandra
A
Ferlini
Paolo
P
Bonaldo
Paolo
P
Bernardi
D017209:Apoptosis / Q000187:drug effects; D002648:Child; D002675:Child, Preschool; D024142:Collagen Type VI / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053580:Muscle Strength / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009136:Muscular Dystrophies / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D012038:Regeneration / Q000187:drug effects; D012598:Sclerosis / Q000188:drug therapy* / Q000235:genetics
D024142:Collagen Type VI; D004791:Enzyme Inhibitors; D016572:Cyclosporine