Stroke is a leading cause of death and disability, with limited treatment options.
Inflammation in the brain after stroke has been shown to be important in the death of brain cells. Drugs are available that can reduce this inflammation, but more information is needed about how to use these drugs to counter the effects of stroke.
In this project, Professor Allan and colleagues will use their well-established mouse models of stroke to test the effects of these drugs to build evidence for their optimal use.
Stroke is caused by sudden interruption of the blood supply to the brain, due to a clot or bleed. This starves the brain tissue of oxygen and glucose, causing brain cells to die. It is a leading cause of death and disability.
Treatment options for stroke are very limited. For stroke caused by a clot (ischaemic stroke), a drug called tPA can be given. This breaks down the clot, restoring blood flow to the brain. Or the clot can be physically removed. While these treatments can enable recovery, they are not suitable for everyone and at present are only received by one in 10 patients.
For a stroke caused by a bleed (haemorrhagic stroke), no treatments have been shown to improve outcomes.
We need to find new treatments that can be given to a greater number of stroke patients, including those with both clots and bleeds.
Professor Allan and others have shown inflammation in the brain after stroke contributes to the death of brain cells. It is possible, therefore, that drugs that reduce inflammation could limit brain damage after stroke, representing a possible new treatment option.
Professor Allan and team have investigated this using a drug called anakinra, which reduces the amount of brain damage in animals with experimental stroke, leading to better recovery of the animals. It is already used in the treatment of other diseases in humans and has been tested in small numbers of stroke patients, with both clots and bleeds. These human trials confirmed that anakinra can reduce inflammation. However, evidence from one trial suggested that anakinra and tPA might not work well when given together. Testing in animals, the team discovered potential negative interactions between the two drugs, reducing beneficial effects.
In this project, the team set out to address two key research questions: firstly whether it is better to give anakinra before rather than after tPA; and secondly, whether another anti-inflammatory drug (isunakinra) is more effective than anakinra in reducing brain damage after stroke, and does not have the same problems when given with tPA.
To address these questions, they are using well-established mouse models of stroke which enable them to mimic the effects of stroke and test the effects of different treatments by using established measures of brain damage.
This project has high potential for patient benefit. Anakinra and isunakinra are both approved for clinical use and can be rapidly repurposed for use in the treatment of stroke and other acute brain injuries. This work will add crucial evidence about how they can best be used to treat the effects of stroke and minimise brain damage.
This work could help people like Andy, who was given just a 5% chance of survival when he suffered a massive stroke during minor surgery and has fought long and hard to overcome the effects of the damage to his brain.
Professor Stuart Allan has worked on brain injury for over 25 years and is recognised internationally for his work. With colleagues in Manchester, including co-investigator Professor Craig Smith, he has led research that demonstrated the importance of inflammation in stroke, leading to clinical trials of anakinra.
Acquired brain and spinal cord injury (including stroke) is one of our current research priorities, reflecting the large unmet need in this area. Our aim is to fund research to advance understanding of how to promote repair of the brain and spinal cord following injury.
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