Grants - Translational Grants - New York - 2021

Adrian Krainer, PhD

Funded by the Dick Vitale Pediatric Cancer Research Fund

We aim to develop a novel and effective therapy for a lethal pediatric brain cancer (diffuse midline glioma, DMG). No effective treatment for DMG currently exists. This cancer arises when a mutation appears in a gene called H3F3A, causing it to produce a toxic protein. The mutant protein makes cells grow unchecked, forming a tumor in an inaccessible brain region and eventually killing the patient. Each of our genes makes RNA—so-called messenger RNA (mRNA)—and the mRNA is then read in another part of the cell to make the protein encoded by that gene. The technology we use, called “antisense”, allows us to target the mRNA made from a gene, and either destroy it or change it. Either way, the toxic protein is no longer made, and because the tumor cells require it for growth, they stop growing and die or change into normal cells. Once our antisense drug is developed, it will be injected into the fluid surrounding the spinal cord, allowing it to reach the brain tumor. Another gene, called H3F3B, encodes the same protein as H3F3A, so our method will get rid of the defective protein but not the normal protein. Therefore, the drug should not harm normal tissues outside the tumor. We will design, test, and perfect our antisense approach using cells derived from DMG tumors, and mouse models of this brain cancer. If this project is successful, the resulting antisense drug will undergo further safety tests, in preparation for clinical trials involving DMG patients.