The University of Texas Southwestern Medical Center awarded Dr. Joseph J. Pancrazio $1,971,800 for his research on Brain Glucose Deficiency: Mechanisms and Modulation. This project aims to create the metabolic and neurophysiological tools to explain the contradiction of patent reductions in glucose accumulation in specific brain areas with the help of diagnostic positron emission tomography for dementia or epilepsy disorders by using the model system of glucose transporter 1 (GLUT1) deficiency (G1D). The conceptual framework of G1D is based on three postulates that apply to a growing number of disorders: One can detect these mechanisms at work in affected individuals non-invasively; two, these mechanisms can be observed at play in affected individuals; and three, metabolic failure leads to preferential inhibitory (as opposed to excitatory) neuron malfunction, which modifies particular brain circuit activity.

This aim will be accomplished by testing and characterizing the interrelation between metabolism and excitability in a G1D mouse model. Fluid downstream from glucose to neurotransmitters will then be measured with neurophysiological activity in people. In addition, further testing will be conducted on the gene of interest (GOI) and LGR in the Mechanistic Trial, which will be based on a mechanism-based testing framework commonly used for metabolic interventions. In collaboration with project leaders and UT Southwestern Medical Center, Dr. Joseph J Pancrazio of the Office of Research and Innovation has coordinated the development of mechanisms and outcomes across the entire biological scale, including molecular flux and cross-reconversions to cell, thalamic circuit, behaving mouse and human brain. With a successful outcome and effective proposed method, this project will deliver the conceptual and methodological foundation to develop the assessment of other thalamocortical illnesses and the mechanistic investigation of metabolic treatments in various forms of epilepsy and dementia.