Prednisone reduces muscle degeneration in dystrophin-deficient Caenorhabditis elegans.
Duchenne muscular dystrophy is a degenerative muscular disease caused by mutations in the dystrophin gene. There is no curative treatment against Duchenne muscular dystrophy. In several countries, the steroid prednisone (or analogs) is prescribed as a palliative treatment. In the model animal Caenorhabditis elegans, mutations of the dys-1 dystrophin-like gene lead to a muscular degenerative phenotype when they are associated with a mild MyoD mutation. This cheap and fast-growing model of dystrophinopathy may be used to screen for molecules able to slow muscle degeneration. In a blind screen of approximately 100 compounds covering a wide spectrum of targets, we found that prednisone is beneficial to the C. elegans dystrophin-deficient muscles. Prednisone reduces by 40% the number of degenerating cells in this animal. This result is a proof-of-principle for the use of C. elegans as a tool in the search for molecules active against the effects of dystrophin-deficiency. Moreover, since C. elegans is not susceptible to inflammation, this suggests that prednisone exerts a direct effect on muscle survival.
Gaud
Aurélie
A
CGMC, CNRS-UMR 5534, Université Lyon1, 43 bld du 11 Novembre, 69622 Villeurbanne cedex, France.
Simon
Jean-Marc
JM
Witzel
Thomas
T
Carre-Pierrat
Maité
M
Wermuth
Camille G
CG
Ségalat
Laurent
L
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D016189:Dystrophin / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics; D009132:Muscles / Q000187:drug effects; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000378:metabolism; D009154:Mutation; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics; D011241:Prednisone / Q000627:therapeutic use*; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics
D000893:Anti-Inflammatory Agents; D029742:Caenorhabditis elegans Proteins; D016189:Dystrophin; D009124:Muscle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C066645:HLH-1 protein, C elegans; D011241:Prednisone