Fontenay aux Roses
Validation of molecular neuroimaging biomarkers in Huntington's disease in view of therapeutic trials targeting the Krebs cycle
Energy defects in Huntington disease (HD) would constitute extremely informative imaging biomarkers of disease progression and readouts in clinical trials. Our translational project aims at measuring dynamic parameters of brain energy metabolism in a transgenic rat model and in affected and presymptomatic HD carriers using MR spectroscopy (MRS). Methodological breakthroughs will include the determination of the synthesis rate of phosphocreatine using saturation transfer 31P MRS, the turnover of the Krebs cycle using 13C MRS, and the establishment of brain maps of pH and glutamate using Chemical Exchange Saturation Transfer (CEST). Likewise, Partners 1 and Partner 2 will assemble their unique MRS setups and wellrecognized expertise in HD. Through the implementation of cutting-edge MR methods, we will gain critical insight on the mechanisms underlying brain energy defects in HD and identify functional biomarkers to be used in clinical trials such as those targeting the Krebs cycle.