Awarded Grants

Awarded Grants

MDBR, GLUT1 Million Dollar Bike Ride MDBR, GLUT1 Million Dollar Bike Ride

Defining the cellular site of action of the Glut1 protein in Glucose Transporter 1 deficiency syndrome.

Umrao Monani

Columbia University

$46,858

Awardee: Umrao Monani

Institution: Columbia University

Award Amount: $46,858

Final Report Summary:

Glut1 DS is a debilitating pediatric brain disorder for which there are limited treatment options.  An important aspect of our work is to explore Glut1 repletion as a means to new treatments for Glut1 DS.  We previously showed that repletion is indeed effective in treating a Glut1 DS mouse model.  Translating these findings into a treatment for the human patient requires defining precisely which cells one must target in repletion therapies.  We hypothesized that brain endothelial cells are one such cell-type.  Our results from this MDBR project suggest that this is indeed the case.  Using a mouse model of Glut1 DS we have shown that introducing a Glut1 mutation specifically in brain endothelial cells triggers all of the major disease characteristics of Glut1 DS.  Moreover, our study reveals a specific type of brain endothelial cell – the tip cell – as being especially vulnerable to Glut1 mutations.  Tip cells are important in enabling the cerebral capillaries to proliferate and develop during the early postnatal period of life.  Reduced Glut1 within them prevents them from proliferating and giving rise to new blood vessels. This effect likely explains the inability of the Glut1 DS brain to extract adequate energy (glucose) from the blood circulation to sustain the nutritional needs of brain neurons.  This, in turn, provides one plausible basis for the neurodevelopmental delay and cognitive dysfunction in Glut1 DS. 

Our study has also confirmed a previous notion of the temporal requirements for Glut1.  The transporter is especially critical in the young postnatal brain when blood capillaries proliferate and neuronal circuits are established. Once the full complement of cerebral blood vessels and neuronal circuits are established, the requirements for Glut1 wane.  These results have important implications for future therapies and imply that treatments may not have to be chronic.  Finally, our investigation has revealed an important mediator of low Glut1 in the brain.  The mediator, a neurotrophic factor that is known to be important for neuronal health and survival, is greatly reduced in the Glut1 DS brain.  Restoring this factor may therefore constitute a novel or adjunct means of treating Glut1 DS in the future. 

Read More
MDBR, CADASIL Million Dollar Bike Ride MDBR, CADASIL Million Dollar Bike Ride

Pericyte contractility in CADASIL

Fabrice Dabertrand

University of Colorado Denver Anschutz Medical Campus

$81,951

Awardee: Fabrice Dabertrand

Institution: University of Colorado Denver Anschutz Medical Campus

Award Amount: $81,951

Read More