The genetic defect in Huntington's disease leads to metabolic dysfunction, which is critical in causing neurodegeneration. Creatine administration can ameliorate the defects.
1. To utilize 13C glucose to assess whether there are metabolic defects in Huntington's disease.
2. To determine whether oral adminstration of creatine can attenuate the metabolic defects.
After optimization of the 13C MRS techniques discussed above (D1.2, D3.2) in phantoms and volunteers (using natural abundance measurements), we will study TCA cycle labeling dynamics using 13C-labeled glucose infusion in patients we have selected with high repeat numbers (>50) and in age-matched controls. The glucose infusion protocol will be performed using a glucose clamp with an initial bolus of 99% labeled [13C]-glucose as modified from the procedure (De Stefano et al., 1979) and reported (Gruetter et al., 1994; Gruetter et al. 1996; Beckmann et al., 1991). The initial bolus will be 20-30 g of glucose, and will be delivered after injection with somatostatin to suppress endogenous insulin secretion. Spectra will be acquired using a large voxel in superior frontal cortex with a surface coil.