Innovative Treatment Shows Promise in Reducing Brain Damage Post-Stroke in Mice

Researchers from the University of Cambridge have developed a novel drug that could significantly mitigate brain injury resulting from strokes. This groundbreaking study, published in Cardiovascular Research, demonstrates that the drug, a form of acidified disodium malonate (aDSM), administered alongside mechanical thrombectomy, can decrease brain tissue damage by up to 60% in mouse models.

Stroke affects approximately 25% of individuals during their lifetime, typically caused by a blood clot obstructing oxygen flow to the brain. The immediate removal of the clot via mechanical thrombectomy—the insertion and retrieval of a device through a blood vessel—remains the primary treatment. However, a complication known as ischemia-reperfusion injury can worsen outcomes. When blood flow resumes abruptly, it can trigger a surge of harmful free radicals generated within mitochondria, the energy-producing structures of cells, leading to further neuronal damage.

The Cambridge team elucidated that during oxygen deprivation, a chemical called succinate accumulates in the brain. Rapid oxidation of succinate upon reperfusion accelerates free radical production, exacerbating tissue injury. Their innovative approach involves administering malonate, which blocks the oxidation of succinate, thereby reducing free radical formation.

By slightly acidifying malonate, researchers improved its ability to cross the blood-brain barrier, allowing for quick delivery during the critical reperfusion phase. In mouse experiments, treatment with aDSM significantly lessened brain damage, highlighting its potential to improve stroke recovery.

Lead researcher Dr. Jordan Lee emphasized that this method encourages less neuronal death, which correlates directly with better functional outcomes for stroke patients. With increasing adoption of mechanical thrombectomy in healthcare, integrating aDSM could enhance recovery rates.

The research team has established Camoxis Therapeutics, aiming to advance this treatment into clinical trials. Professor Mike Murphy noted that if successful, this strategy could have broader implications for other ischemic injuries such as heart attacks, organ transplants, and resuscitation efforts.

This innovative research offers hope for more effective stroke therapies in the future, potentially transforming acute stroke management and patient prognosis.