Zebrafish based small molecule screens for novel DMD drugs
- Authors
- Kawahara, G., and Kunkel, L.M.
- ID
- ZDB-PUB-130607-8
- Date
- 2013
- Source
- Drug Discovery Today: Technologies 10(1): e91-e96 (Journal)
- Registered Authors
- Kawahara, Genri, Kunkel, Louis M.
- Keywords
- none
- MeSH Terms
- none
- PubMed
- 23646060 Full text @ Drug Discov. Today Technol.
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.