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Twenty-year research could herald new stroke treatment

Tuesday July 31st, 2012

British scientists believe their 20-year search to find a drug that can dramatically limit brain damage in stroke patients may soon be a reality after “promising” results.

Anakinra (IL-1Ra), which is already used for rheumatoid arthritis in experimental studies of stroke, was found to block the naturally occurring protein interleukin 1, which is a key cause of brain injury following a stroke.

Building on previous research, scientists at the University of Manchester, UK, induced a stroke in rats with stroke risk factors such as obesity, insulin resistance and atherosclerosis, as well as healthy rats and older ones. They were injected with the drug IL-1Ra, or a placebo for comparison, under the skin.

Professor Dame Nancy Rothwell, Professor Stuart Allan and their team described the results as “startling”: MRI scans revealed that the rats given IL-1Ra up to three hours after the stroke had about half the brain damage of the placebo group.

“This is the first time that we are aware of a potential new treatment for stroke being tested in animals with the same sort of diseases and risk factors that most patients have,” says Prof Rothwell, whose study is published in the Journal of Cerebral Blood Flow and Metabolism.

“The results are very promising and we hope to undertake further clinical studies in stroke patients soon.”

Interleukin 1 encourages inflammation in the area of the brain affected by stroke, which sends out signals to attract white blood cells and to switch on microglia cells in the brain.

Because the barrier surrounding the brain is weakened by stroke, white blood cells find it easier to enter the brain and kill nerve cells and worsen the injury. The increasing presence of the cells also explains why the damage in the brain gets worse over time following a stroke.

IL-1Ra also reduces the amount of damage to the blood-brain barrier following a stroke so the harmful cells can’t enter the brain.

Professor Stuart Allan at The University of Manchester, said: “This drug has real potential to save lives and stop hundreds of thousands of people being seriously disabled by stroke. This really could be the treatment for stroke that we’ve been looking for over the past two decades.”

A phase 2 trial with a small number of patients has yielded encouraging results. It is hoped a much larger clinical trial will demonstrate the effectiveness of IL-1Ra in reducing brain damage in stroke patients and that eventually it will become the standard treatment.

Delayed administration of interleukin-1 receptor antagonist reduces ischemic brain damage and inflammation in comorbid rats. Allen S, Rothwell N et al. Journal of Cerebral Blood Flow & Metabolism. July 2012. doi: 10.1038.

Tags: Brain & Neurology | Pharmaceuticals | UK News

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