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.

Pre-clinical trials in Duchenne dystrophy: what animal models can tell us about potential drug effectiveness

DE LUCA, Annamaria;PIERNO, Sabata;LIANTONIO, ANTONELLA;CONTE, Diana
2002-01-01

Abstract

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.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/110613
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 11
  • Scopus 20
  • ???jsp.display-item.citation.isi??? 18
social impact