Funded Research

Prevention and Treatment of Hepatic Steatosis Throught Selective Targeting of GLUT8
Principal Investigator(s):
  • Brian DeBosch, M.D., Ph.D. Pediatrics
  • Paul Hruz, M.D., Ph.D. Pediatrics Visit Website
Status:
Active
Center(s):
  • Center for Metabolism and Immunity
Award Mechanism:
Interdisciplinary Research Initiative
Project Period:
2/1/2017 - 1/31/2020
Total Amount:
$450,000

Brief background of the proposal and its relevance to the CDI’s objectives

Non-alcoholic fatty liver disease (NAFLD) is a common and serious disease characterized by excess liver fat accumulation. NAFLD affects one billion individuals worldwide and is a leading cause of liver failure and transplantation. The most rapidly increasing population acquiring this disease is children, but safe and effective treatments have been lacking. The goal of this project is to identify novel therapies for NAFLD based on targeted inhibition of the sugar transporter, GLUT8. This will be accomplished using a novel drug candidate screen for compounds that have high affinity and selectivity for GLUT8. The hypothesis that selective GLUT8 inhibition reverses fat accumulation in the liver will be examined.

Proposed specific aims

·         Identify novel selective small molecule GLUT8 inhibitors.

·         Define the safety profile of new and previously identified GLUT8 inhibitors by measuring their effects on glucose metabolism and liver fat accumulation.

·         Demonstrate mechanisms by which a candidate GLUT8 inhibitor, “Compound G8i04”, activates

adaptive liver responses.

Potential impact on child health

Identifying selective, high-potency small molecule GLUT8 inhibitors and validating their efficacy against

NAFLD in pre-clinical models will justify full-scale drug development with extension to human clinical trials.