Medical Student Research Fellowship for Summer 2011

Mentor:                       Juan M. Pascual, MD, PhD                      
Department:             Neurology    
Room number:         ND4.214A
Mail Code:                 8813
Phone number:        214-648-5818
E-mail:                       Juan.Pascual@UTSouthwestern.edu
Project title:                           Structural and functional MRI study of human glucose transporter encephalopathy

Human subjects IRB approved project number (where applicable): Pending

Animal subjects IRB approved project number (where applicable):  N/A

Project Type (patient-based research, animal-based research, or basic research; this characterization is only to permit a general classification for grouping similar types of projects)

Human research

Brief Description of Project:
The purpose of this study is to characterize clinical, analytical and MR Spectroscopy (MRS) indicators (cerebral metabolic rate and metabolite abundance) of a prototypic glycolytic defect: glucose transporter type I deficiency (GD), a childhood-onset encephalopathy associated with normal lifespan, permanent disability and responsiveness to increased brain fuel availability. An additional goal is to treat GD with citric acid cycle precursors derived from triheptanoin, a medium-chain triglyceride containing three odd-carbon-number (i.e., 7-carbon) fatty acids that leads to increased citric acid cycle flux and replenishment of intermediates via the formation of odd-carbon-number ketone bodies that are readily taken up by brain and muscle. Neurological performance, analytical and MRS outcome measures will be used to establish therapeutic efficacy.
This proposal is a single-site (Rare Disorders Clinic located at the Children’s Medical Center Dallas Ambulatory Care Pavilion Medical Center) open label clinical trial. MRS will be conducted at the Clements Advanced Imaging Research Center. 10 Glut1 deficient children will participate in all the procedures. Because we have established the dosing, tolerability, safety profile and pharmacokinetics of triheptanoin in man (FDA IND 59303: “Dietary therapy for inherited disorders of mitochondrial fat oxidation and glycogenoses”, responsible investigator Dr. Roe and subsequent expansion to “glycolytic defects” and cross-referencing to UT Southwestern Medical Center with responsible investigator Dr. Pascual) and because the triglyceride has no discernible effects on normal metabolism as assessed by comprehensive analytical methods, no normal participants will be studied for the analytical part of the proposal. However, age-related normal participants will be studied for comparison with MRS measurements. While there are no significant natural sources of triheptanoin or of odd-carbon number fatty acids in nature, triheptanoin is readily available commercially (generally in bulk quantities for use as a food additive).

Previous Research Activities or Publications with Medical Students:
SURF mentor: 2009 and 2010