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Twenty-year search for a drug for the treatment of stroke was crowned with success
Last reviewed: 16.10.2021
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A team of scientists at the University of Manchester, UK, presented a drug that dramatically reduces the degree of brain damage in stroke patients. Phase 2 trials on a small number of patients gave encouraging results. Scientists hope that more extensive clinical trials will confirm the effectiveness of the drug and eventually it will become a standard method of treatment.
The last 20 years of his work, Professors Dame Nancy Rothwell and Stuart Allan and their group have devoted to studying how to reduce the degree of brain damage after a stroke.
Their latest work is based on previous studies, but is radically different from them in that, along with healthy and old rats, animals with risk factors for stroke such as obesity, insulin resistance and atherosclerosis were used. This means that scientists have a much greater chance of reproducing the results on stroke patients.
Scientists were testing the effectiveness of the drug Anakinra (IL-1Ra), which is already used to treat rheumatoid arthritis.
The mechanism of action of IL-1Ra is to block the function of the natural protein interleukin-1. Scientists from the University of Manchester have determined that this molecule is the main cause of post-stroke brain damage.
Interleukin-1 stimulates the inflammatory process in the region of the brain affected by a stroke. It is a signal for attracting leukocytes and activation in the brain of microglial cells. Since the permeability of the blood-brain barrier after a stroke increases, it becomes easier for leukocytes to penetrate the brain. But instead of helping the inflamed area, they actually kill the nerve cells and aggravate the state of the brain tissue. The presence of an increased number of these cells also explains why in the post-stroke period the state of the damaged brain progressively worsens.
IL-1Ra and placebo were administered to rats under the skin after a stroke induced by them. Which animals received IL-1Ra, and which placebo, even the researchers themselves did not know. (This testing scheme is used in clinical trials of drugs.)
The results of the experiments astounded the scientists. Magnetic resonance imaging showed that if rats received IL-1Ra for the first three hours after the stroke, their brain damage was half that of the placebo group.
In addition, IL-1Ra reduces the degree of post-stroke damage to the blood-brain barrier, which prevents the penetration of unwanted cells into the brain. In recent experiments, IL-1Ra reduced the degree of damage to the blood-brain barrier by 55% in healthy rats and by 45% in rats with diseases-risk factors for stroke. In all groups, the drug reduced the number of activated microglia cells by 40% compared with the placebo group.
The only drug available today for the treatment of stroke patients is the tissue plasminogen activator (ATP). However, it can be prescribed only to patients with ischemic stroke. To determine which type of stroke a patient needs, brain scanning is necessary (which is why it is so important to deliver it to the hospital as soon as possible). In addition, ATP is effective only when administered within a few hours after a stroke.
Professor Allan hopes that IL-1Ra can be used in both ischemic and hemorrhagic strokes. The main condition for success, however, remains the same - the drug must be injected immediately.
"This drug has a real potential to save lives and prevent the disability of hundreds of thousands of people. It really can be the treatment for a stroke that we've been looking for over the last two decades, "the scientist comments on the results of his work.