Examining potential drug therapies for muscular dystrophy utilising the dy/dy mouse: I. Clenbuterol

As a potent promoter of muscle growth, clenbuterol has been proposed as a treatment for muscle wasting diseases. Thus, the effects of clenbuterol on dystrophic skeletal muscle was examined. Male dystrophic (dy/dy) mice aged 4-5 weeks were treated with clenbuterol for 3 weeks, and the isometric contractile, fatigue and histochemical properties of the slow-twitch soleus and fast-twitch plantaris muscles measured. Muscles of dystrophic animals produced lower forces, contracted more slowly and exhibited greater fatigue resistance than age-matched normal animals. Dystrophic soleus muscles also had higher proportions of type I fibres than normal mice. Clenbuterol significantly reduced the natural death rate of dystrophic mice, as 3 of 11 untreated animals died prior to completion of the 3-week experimental period, whereas none of the 9 clenbuterol-treated animals died. Clenbuterol treatment significantly increased the relative mass (P<0.001) and relative tetanic force production (P<0.01) of the soleus of dystrophic animals, most likely due to increases in protein accretion and improved regeneration. The plantaris of clenbuterol-treated dystrophic animals also exhibited higher mass (P<0.05) and higher absolute forces than untreated mice. The results from this study show that clenbuterol could be a valuable adjunct to treatments of muscle wasting diseases such as muscular dystrophy. (C) 1998 Elsevier Science B.V.