Therapeutics: Peroxisome proliferation activated receptor delta (PPARδ)

Mouse studies suggest PPARδ agonists could help treat HD. PPARδ activity and mitochondrial membrane potential were lower in primary cortical neurons from a mutant huntingtin (HTT) mouse model of HD than from normal mice. In the HD neurons, viral vector-mediated overexpression of PPARδ or a tool compound that agonizes PPARδ increased mitochondrial membrane potential and decreased apoptosis compared with empty vector or vehicle. In another mouse model of HD, the PPARδ agonist KD3010 decreased neurological and motor dysfunctions and increased survival compared with vehicle. Next steps could include testing PPARδ agonists in other HD models.

Kalypsys Inc. has KD3010, an oral PPARδ agonist, in Phase I testing to treat diabetes and non-alcoholic steatohepatitis (NASH)...