Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about potential drug effectiveness.
The symptomatic pharmacological therapy of Duchenne dystrophy is poor, glucocorticoids being the sole compounds showing a certain efficacy, although their use is restricted by serious side effects. Pre-clinical trials of prompt-to-use drugs need reliable animal models of the human disease to predict drug effectiveness in patients. The exercised mdx mouse develops a typical pattern of muscle weakness in vivo, which has already been used as an index on which to evaluate drug effectiveness. We have demonstrated that the macroscopic conductance to chloride ion, an index of degeneration-regeneration events occurring in mdx mouse muscles, is specifically impaired by a chronic exercise protocol and is sensitive to the action of in vivo administered drugs acting either by stimulating regeneration (insulin-like growth factor-1 and steroids) or by counteracting calcium-induced degeneration or inflammation (Taurine and steroids). The monitoring of conductance to chloride ion also allows the evaluation of false positive compounds, effective on mouse strength in vivo but not at muscle level, and the functional correlation with other cellular parameters.
Sezione di Farmacologica, Dipartimento Farmacobiologico, Facoltà di Farmacia, University of Bari, Via Orabona 4, 70125 Bari, Italy. adeluca@farmbiol.uniba.it
Annamaria
A
De Luca
Sabata
S
Pierno
Antonella
A
Liantonio
Diana
D
Conte Camerino
D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D018118:Chloride Channels / Q000187:drug effects* / Q000378:metabolism*; D018450:Disease Progression; D016189:Dystrophin / Q000172:deficiency*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D051379:Mice; D018101:Mice, Inbred mdx; D023421:Models, Animal; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013654:Taurine / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D018118:Chloride Channels; D016189:Dystrophin; D013654:Taurine; D007334:Insulin-Like Growth Factor I