PATHOGENESIS AND THERAPY OF PRIMARY COENZYME Q DEFICIENCY

Coenzyme Q is a small lipophylic molecule which is essential for energy production in cells. Some patients, mostly children, cannot synthesize this substance because of a genetic defect. This disease is called CoQ deficiency and is a severe and oftet fatal clinical condition. Our group has been studying CoQ deficiency since 2004. We participated to the discovery of the first genetic defect responsible for this disease and we have demonstrated that it is possible to cure these patients by treating them with high doses of coenzyme Q. However, there are still a number of open issues concerning this disease. Many patients lack a geneic diagnosis and we do not know all the genes involved in the biosynthesis of coenzyme Q in humans. Most of all we do not know what is the most appropriate dose of coenzyme Q that must be administered to patients and we have no effective method to monitor therapy. Our proposal is meant to address these issues. We have identified defects in three novel gene in a group of patients with coenzyme Q deficiency. We plan to understand the role of these genes in coenzyme Q biosynthesis and to confirm that the alterations we have detected ar actually the cause of the disease in our patients. We will also study how the biosynthesis of coenzyme q is regulated. Finally we will use a specific mouse strain which has coenzyme Q deficiency to optimize our therapeutic protocols. Our results will provide clear benefit to patients, because we will improve the diagnostic process and the way they are cured. Overall, we will provide patients with a credible therapeutic option, a unique situation for mitochondrial disorders, and for genetic diseases in general.