13C Glucose Metabolism in Huntington’s Disease and Assessment of Creatine for Therapy

M. Flint Beal, M.D.

Cornell University , New York, NY

Grant Program:

David Mahoney Neuroimaging Program

Funded in:

December 1998, for 3 years

Funding Amount:

$100,000

Investigator Biographies

M. Flint Beal, M.D.

Chairman and Neurologist-in-Chief, New York Presbyterian Hospital – Weill Medical College of Cornell University

Hypothesis

Hypothesis:
The genetic defect in Huntington's disease leads to metabolic dysfunction, which is critical in causing neurodegeneration. Creatine administration can ameliorate the defects.

Goals:
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.

Methods:
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.