Funded Grants

Grantee: MD Anderson Cancer Center
Project Lead: VIDYA GOPALAKRISHNAN, PHD
Grant Title: Repurposing Migraine Treatments for DIPG
Grant Type: UKF Seed Grant and 3 renewals
Year Awarded: 2019, 2020, 2021, 2022, and 2023
Amount: $250,000
Duration: 5 years

Summary: Diffuse Intrinsic Pontine Glioma (DIPG) is an incurable pediatric brain tumor. It represents nearly 10% of all pediatric central nervous system tumors. Approximately 80% of human DIPGs exhibit a recurrent H3K27M mutation and 75% of these are found in the H3F3A gene, which encodes histone H3.3. The less than two-year survival rate in patients highlights the desperate need for treatments. 

With the support of the Uncle Kory Foundation, Dr. Gopalakrishnan and her team at The University of Texas MD Anderson Cancer Center in Houston, Texas, have discovered that a protein called REST is expressed at higher levels in DIPG tumors than in normal tissue and is required for DIPG growth. A REST-context specific chemical screen using re-purposable drugs identified candidates that target cell-surface receptors controlling cell-cell communication in the nervous system as having potential for therapeutic evaluation. Pre-clinical studies with cell culture and mouse orthotopic models of DIPG confirmed that DIPG cells harboring the H3K27M mutation were indeed more sensitive to these drugs than DIPG tumors expressing wildtype histones and that REST elevation further increased their drug sensitivity. Future studies will be two-pronged. The first will be directed at clinical translation of the above findings through Phase I/II studies. The fact that these agents are already used in children to treat neurological disorders will facilitate our application to the FDA requesting their study in patients with DIPG. The second will involve multi-omics studies to understand the molecular characteristics of tumor cells that respond and those that don’t. This will allow us to develop combination treatments to target the non-responders.

The Gopalakrishnan group are very grateful to the Uncle Kory Foundation and their team for their support in getting a high-risk project off the ground!