Targeting DNA repair for neuroinflammation in stroke

Abstract

Acute inflammation of the brain after stroke and head trauma presents a serious health issue affecting millions of patients each year in the U.S. This inflammation causes adverse health outcomes both on the short and long term, and current treatments are insufficient, and in stroke, limited to vascular interventions with finite therapeutic time windows. Prompted by this need, we are pursuing a novel therapeutic target for this neuroinflammation. We are targeting the enzyme OGG1, a DNA repair enzyme that acts both in the nucleus and in mitochondria; multiple lines of biological evidence now support this protein as a potentially important controller of acute inflammatory responses. In this project, we will test the effects of a biologically active small molecule OGG1 inhibitor (SU0268), developed recently at Stanford, in mouse models of stroke where the elaboration of inflammation drives cerebral injury. The results are expected to validate the effectiveness of inhibiting OGG1 in acute inflammatory responses in the brain, and if the approach proves efficacious, we will work to test this drug (or a close analog) in clinical trials.  

This project is jointly supported by Wu Tsai Neurosciences Institute and SPARK