Weekly oral prednisolone improves survival and strength in male mdx mice.
Although corticosteroids alleviate weakness in mdx mice, no long-term treatment has determined whether this benefit is maintained. We studied mdx mice forelimb grip strength and fatigue from 3 through 84 weeks and followed survival through 104 weeks. The mdx mice were given twice weekly oral prednisolone (5 mg/kg) beginning at 3 or 4 weeks. Treated mdx mice survived longer than untreated mice. Between 3 and 10 weeks, treated and untreated mdx mice had similar strength. Between 10 and 24 weeks, strength and strength per gram body weight declined more slowly in treated than untreated mdx mice. Between 24 and 84 weeks, treated and untreated mdx mice declined in strength at the same rate, although treated mice remained stronger. Forelimb grip fatigue was present in untreated mdx mice at all time-points compared to wild-type and was not changed significantly by treatment. We have demonstrated long-term benefit of oral prednisolone in the mdx mouse model of Duchenne muscular dystrophy (DMD). As corticosteroids remain the most validated long-term treatment of DMD, this work may allow for better prediction of synergistic treatments likely to translate to effective improvement for boys with this progressive muscular dystrophy.
Keeling
Richard M
RM
Department of Neurology, Box 8111, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
Golumbek
Paul T
PT
Streif
Elizabeth M
EM
Connolly
Anne M
AM
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D016189:Dystrophin / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018763:Muscle Fatigue / Q000187:drug effects / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018908:Muscle Weakness / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000503:physiopathology; D011239:Prednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D015996:Survival Rate; D016896:Treatment Outcome
D000893:Anti-Inflammatory Agents; D016189:Dystrophin; D011239:Prednisolone