Researchers, led by Parama Paul, PhD, screened an FDA-approved compound library for drugs that promote nuclear export of histone deacetylase 5 (HDAC5) they believed would indicate therapeutic potential for treating ADPKD. Unexpectedly, domperidone and loxapine succinate, dopamine receptor antagonists, were potent promoters of HDAC5 export in renal cells. Further, domperidone slowed growth of cysts, reduced the number of cysts, and increased body weight and activity in a mouse model of ADPKD. The findings were reported in PlosOne.
The researchers said, “These results suggest that HDAC5 nucleocytoplasmic shuttling may be modulated to impede disease progression in ADPKD, and uncovers an unexpected role for a class of dopamine receptors in renal epithelial morphogenesis.”