Grant: Emerging Team Grant: From Genes to Proteins, Cells, Tissues and Patients

Leigh syndrome French Canadian Type (LSFC) is an inherited metabolic disorder that usually kills children before 4 years of age. First described in 1993 by Dr Morin & colleagues, LSFC is characterized by an energy deficit and deadly lactic acidosis episodes commonly referred to as "crisis". The current incidence of this disease is 1/2000 and it is highly prevalent in the north-eastern region of Quebec where the number of carriers is estimated at 1/23. In 2003, Dr Rioux & colleagues identified the mutations responsible for the LSFC in the LRPPRC gene thereby enabling prenatal screening. The challenge is now to translate this information into treatment. Currently, therapeutic options for LSFC children undergoing crisis are practically nonexistent due to our lack of understanding of the (1) function of the normal LRPPRC protein, and (2) circulating factors that trigger the crisis and precipitate death. Hence, we have formed a multidisciplinary team of basic and clinical researchers, which includes Drs Morin and Rioux, and headed by Dr Des Rosiers, to tackle these issues using state-of-the art technologies. The ultimate goal of this team's research project is to identify circulating biomarkers for early detection and molecules for effective treatment in order to improve survival of LSFC patients undergoing a lactic acidosis crisis without any detrimental consequences such as brain injury. Our team includes pediatricians who treat children with inborn errors of metabolism such as the LSFC and works in close partnership with the Lactic Acidosis Association to insure rapid translation of research results to the target population. Anticipated findings of the proposed research go beyond LSFC patients as they may apply to other conditions involving mitochondrial energetic defects including common chronic diseases such as diabetes and heart failure.