Manuel Schiff and Clément Pontoizeau
MSUD is a rare (1 in 185,000 live births) genetic disorder due to the dysfunction of an enzyme involved in the degradation of an amino acid called leucine. As a consequence, leucine and its derivatives accumulate in the whole organism giving rise to coma especially in the neonatal period.
Long-term treatement of MSUD consists of a life-long and very strict low-protein diet. As liver significantly contributes to leucine degradation, an alternative therapy to this strict diet is liver transplantation with substantial constraints and risks. The aim of our project is to replace the defective gene in the liver. This will first be tested in MSUD mice after extensive characterization of this animal model (signs of disease, blood parameters) and further in human cells.