Galactosemia is a rare, inherited condition where people cannot metabolize galactose due to mutations in GALT, GALE, and GALK1. The disorder appears in 1 in 40,000 live births and can be fatal if left untreated, but no long-term treatment exists. Although removal of galactose from the diet can prevent death, galactosemia patients still experience intellectual and speech deficits, motor function loss, ataxia, and infertility due to galactose accumulation.
Accumulation of Gal1-p results in a unique form of endoplasmic reticulum stress in fibroblasts of patients with Galactosemia. A small molecule GALK inhibitor can alleviate symptoms of Galactosemia by reducing accumulation of human galactose. GALK inhibitor leads have been identified for testing in animal models. Patient cell lines, crystal structure data, and animal models for Galactosemia are available for rapid development of an IND enabling candidate.