Zebrafish based small molecule screens for novel DMD drugs.
Recently, a number of chemical and drug screens using zebrafish embryos have been published. Using zebrafish dystrophin mutants, we screened a chemical library for small molecules that modulate the muscle phenotype and identified seven small molecules that influence muscle pathology in dystrophin-null zebrafish. One chemical, aminophylline, which is known to be a non-selective phosphodiesterase (PDE) inhibitor, had the greatest ability to restore normal muscle structure and to up-regulate cAMP-dependent protein kinase (PKA) in treated dystrophin deficient fish. Our methodologies, which combine drug screening with assessment of the chemical effects by genotyping and staining with anti-dystrophin, provide a powerful means to identify template structures potentially relevant to the development of novel human muscular dystrophies therapeutics.
Genri
G
Kawahara
Louis M
LM
Kunkel
D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D016189:Dystrophin / Q000235:genetics* / Q000378:metabolism; D004625:Embryo, Nonmammalian; D009132:Muscles / Q000378:metabolism; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D054852:Small Molecule Libraries; D015027:Zebrafish / Q000002:abnormalities / Q000235:genetics*
D016189:Dystrophin; D054852:Small Molecule Libraries