The viability of neurons in the brain depends on a complex series of interconnected biochemical reactions that constitute cellular metabolism. Disruption of these metabolic pathways is associated with neurological conditions, including Alzheimer’s and Parkinson’s. Recent technical advances in the analysis of cellular metabolites mean it is now possible to simultaneously quantify the passage of multiple metabolites through cells over time. We will leverage this metabolomic flux analyses to compare the metabolite profiles of control cells and cells that lack the protein sacsin, which is mutated in ARSACS. We believe disruption of cellular metabolism is likely to be particularly relevant to ARSACS. This is because it has previously been shown that the health of mitochondria, organelles where key metabolic enzymes are located, is reduced in cellular and animal models of ARSACS. Our goal is to define the metabolic changes that occur in sacsin deficient cells as we believe this will elucidate ARSACS disease mechanism and potentially identify targets for therapeutic intervention.

Grant: £37,714

Duration: first year of a 2 year project


Dr. Paul Chapple , Faculty of Medicine and Dentistry
Queen Mary University of London
London UL