Investigation of intertwined relationships between healthy and mutated GLUT1 using FDA approved compounds to identify a therapeutic approach

GLUT1 protein captures and promotes the uptake of energy into the brain in the form of glucose. Mutations in the SLC2A1 gene, the blueprints for making the GLUT1 protein, lead to a metabolic disorder known as GLUT1 deficiency. This homozygous genetic disease does not have a known cure and a ketogenic diet, which is high in fat and low in carbohydrates and protein, is the standard treatment. This diet produces ketone bodies that bypass the GLUT1 defect and cross the blood-brain barrier to fuel the brain. The lack of alternative therapies is partially due to a poor understanding of the mechanisms that regulate GLUT1 biochemical functions. Therefore, a more complete understanding of GLUT1 protein structure and function will help identify new therapies for the treatment of GLUT1 deficiency. We will investigate if the abnormal GLUT1 protein has any effect on the function and proper localization at the plasma membrane of the healthy GLUT1. Moreover, we will search for alternative biological pathways that could compensate for the absence of GLUT1 protein. In our analysis we will use chemicals that are already employed for the treatments of other disease. This strategy will potentially allow to reposition a drug offering an alternative therapeutic approach.