This project will test a new small molecule that is designed to reduce the activity of the enzyme acid ceramidase, which is the enzyme that synthesizes psychosine. Psychosine is a lipid that accumulates to high levels in the brain of Krabbe disease, a genetic disorder caused by deficiency of another enzyme called GALC, which controls the degradation of psychosine. In the absence of GALC activity, psychosine continues to be produced but not degraded. High levels of psychosine in Krabbe disease cause neuropathology and motor and cognitive declines in infants, juvenile and adult patients. There is no cure for Krabbe disease. Here we will treat animal models of infantile and adult onset Krabbe disease with the small compound singly and in combination with a gene therapy approach to restore the activity of the enzyme GALC, which is deficient in Krabbe disease. We hypothesize that reducing the synthesis of psychosine will improve the metabolism of psychosine, reduce disease burden and neuropathology.

Project financed by ELA up to: 100 000 €