GLPG0492, a novel selective androgen receptor modulator, improves muscle performance in the exercised-mdx mouse model of muscular dystrophy

摘要: Anabolic drugs may counteract muscle wasting and dysfunction in Duchenne muscular dystrophy (DMD); however, steroids have unwanted side effects. We focused on GLPG0492, a new non-steroidal selective androgen receptor modulator that is currently under development for musculo-skeletal diseases such as sarcopenia cachexia. GLPG0492 was tested the exercised mdx mouse model of DMD 4-week trial at single high dose (30 mg/kg, 6 day/week s.c.), results were compared with those from administration α-methylprednisolone (PDN; 1 i.p.) nandrolone (NAND, 5 s.c.). This assessment followed by 12-week dose-dependence study (0.3-30 mg/kg The outcomes evaluated vivo ex functional, histological biochemical parameters. Similar to PDN NAND, significantly increased strength. In acute exhaustion tests, surrogate 6-min walking test used patients, preserved running performance, whereas vehicle- or comparator-treated animals showed significant increase fatigue (30-50%). Ex vivo, all resulted modest but diaphragm force. parallel, decrease non-muscle area markers fibrosis observed GLPG0492- NAND-treated mice. exerted minor effects limb muscles; electrophysiological biomarkers ameliorated extensor digitorum longus muscle. longer confirmed effect strength resistance demonstrated efficacy lower drug doses functional These support interest further studies potential treatment DMD.