New Drug Halves Stroke Brain Damage

Cambridge Scientists Pioneer Therapy to Mitigate Ischemic-Reperfusion Injury

A potential breakthrough in stroke treatment could dramatically reduce brain damage, offering new hope to millions affected annually. Researchers have developed a drug that shows remarkable efficacy in preclinical trials.

Targeting Post-Stroke Injury

Strokes, which strike 15 million people worldwide each year, can lead to death or permanent disability for half of those affected. While treatments exist to restore blood flow, the process itself can cause secondary damage. Scientists at the University of Cambridge have engineered a novel compound designed to counteract this harmful effect. Published in Cardiovascular Research, their findings suggest this drug could slash brain damage by up to 60%.

Understanding the Mechanism

A stroke occurs when blood supply to the brain is interrupted, either by a blockage (ischemic stroke, 87% of cases) or bleeding (hemorrhagic stroke). The critical window following a stroke involves restoring blood flow, often through mechanical thrombectomy. However, this process, known as reperfusion, can overwhelm oxygen-starved brain cells, generating damaging free radicals – a phenomenon called ischemia-reperfusion injury.

Succinate’s Role and Malonate’s Solution

Previous work by the Cambridge team identified succinate accumulation in the brain during oxygen deprivation. Upon reperfusion, succinate rapidly oxidizes, fueling free radical production within cellular mitochondria. The researchers discovered that malonate can effectively block this oxidation. As highlighted by Professor Mike Murphy from the Medical Research Council Mitochondrial Biology Unit, “All of this happens very rapidly, but if we can get malonate in quickly at the start of reperfusion, we can prevent this oxidation and burst of free radicals.”

To enhance delivery across the blood-brain barrier, the team developed acidified disodium malonate (aDSM). In laboratory tests using a mouse model that simulates mechanical thrombectomy, aDSM administered alongside the procedure significantly reduced brain damage associated with reperfusion.

“This approach reduces the amount of dead brain tissue resulting from a stroke. This is incredibly important because the amount of dead brain tissue is directly correlated to the patient’s recovery, to their disability, whether they can still use all their limbs, speak, and understand language, for example,” said Dr Jordan Lee, a postdoctoral researcher involved in the mouse model development.

Promising Future Applications

The efficacy of aDSM in reducing brain damage by as much as 60% is a significant advancement. Researchers are now eager to initiate early-stage clinical trials.

“If it’s successful, this same drug could have much wider applications for other instances of ischemia-reperfusion injuries, such as heart attack, resuscitation, organ transplantation, and so on, which have similar underlying mechanisms,” added Professor Mike Murphy.

This development follows a broader trend in medical research focusing on mitigating secondary injury in critical conditions. For instance, studies have shown that prompt intervention following a transient ischemic attack (TIA), or mini-stroke, can help prevent more severe long-term cognitive decline (News-Medical.net, March 2024).