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Disease models

Zebrafish and cell culture models for arrhythmogenic cardiomyopathy

Zebrafish and cell culture models of arrhythmogenic cardiomyopathy could help drug discovery in the indication. In transgenic zebrafish, a mutation in junction plakoglobin (Jup) linked to arrhythmogenic cardiomyopathy in humans led to cardiac hypertrophy, arrhythmia and heart failure. In the model, chemical screening identified small molecules, including the glycogen dependent kinase 3 (GSK3) inhibitor SB216763, that increased survival at three months compared with no treatment. In cultured neonatal rat ventricular myocytes expressing the mutant Jup, SB216763 decreased apoptosis compared with no treatment and prevented the formation of cellular structural abnormalities. Next steps include confirming the mechanism of action of SB216763 and testing the compound and related molecules in mouse models of arrhythmogenic cardiomyopathy.
GlaxoSmithKline plc's SB216763 has been evaluated in Phase I trials for bipolar disorder.

SciBX 7(28); doi:10.1038/scibx.2014.842
Published online July 24, 2014

Patent pending; available for licensing

Asimaki, A. et al. Sci. Transl. Med.; published online June 11, 2014;
Contact: Jeffrey E. Saffitz, Beth Israel Deaconess Medical Center, Boston, Mass.
Contact: Angeliki Asimaki, same affiliation as above