Pre-clinical screening of drugs using the mdx mouse.

The genetically dystrophin-deficient mdx mouse, with its characteristic and regular exercise-induced loss of strength, is a useful experimental platform on which to screen potential drug therapies in the treatment of some dystrophic diseases. Pharmacological agents of several chemical and functional classes were examined in their ability to reduce the loss of muscular strength in young exercised mdx mice. Therapeutic intervention over the period 4-10 weeks of age was evaluated in weekly tests of whole-body strength. This age period represents the most severe manifestation of disease in these animals. Significant improvements in whole-body strength were brought about by treatment with the immunosuppressive and anti-inflammatory drugs prednisone (at low dose only, 1 mg/kg body weight), pentoxifylline (100 mg/kg) and tinset (100 mg/kg). The anabolic hormone insulin-like growth factor-1 (5 mg/kg), as well as the amino acids/metabolites glutamine (10 mg/kg), glutamine plus alanine (each 10 mg/kg), and creatinine (10 mg/kg) all improved strength test performance. The mdx mouse is a responsive system for the screening of potential therapeutic treatments for the muscular dystrophies.