Why is this research needed?

Strokes can happen for two reasons. In ischaemic (clotting) strokes, a clot blocks a blood vessel. In haemorrhagic (bleeding) strokes, a blood vessel breaks open and blood leaks into the brain tissue.

Bleeding strokes are rarer than clotting strokes, but are much more likely to be deadly or to cause severe disability. Our treatment options for the most common type of bleeding stroke, intracerebral haemorrhage or ICH, are extremely limited.

Dr Nesh Samarasekera says, "The outcomes for people after a bleeding stroke have not improved over the last 30 years. A year after a bleeding stroke about 5 out of 10 people will be dead and another 2 or 3 people out of 10 will be dependent on others for everyday activities."

We are in urgent need of better treatments for ICH, but two things stand in the way. One is that we need a deeper understanding of what is happening in the brain during ICH. The other is that because ICH is both life-threatening and relatively uncommon, it is hard to recruit people to clinical trials for new ICH treatments. During her lectureship, Nesh will look for ways to address both these problems.

What are the aims of this research?

Nesh's focus is on inflammation that happens in the brain shortly after an ICH. Inflammation is generally a helpful part of our immune response, with positive effects like killing off bacteria, breaking down dead cells, and repairing injured cells. However, in ICH, this inflammation can have negative as well as positive effects. Nesh theorises that it is possible to modify the brain's inflammatory response to be of more benefit to ICH patients.

In the first phase of her lectureship, Nesh will be investigating what's going on in the brain after an ICH. She believes that the brain may have different kinds of inflammatory responses depending on which parts of it are affected by the ICH. With her team, she'll examine brain tissue donated by people whose ICHs happened in different parts of the brain to see which cells and molecules are involved in inflammation. One or more of these molecules could be a target for a drug that can modify the inflammation.

Next, Nesh and her team will work on identifying drugs that are already used for other conditions which could also work on these target molecules. They’ll then narrow down which drugs are worth testing in a clinical trial by looking at the quality of the evidence – for example, how many studies they’ve been tested in and whether they’re safe to give to someone who’s having an ICH.

Nesh and her team think that brain swelling is a marker of inflammation that is happening in the brain after ICH. They will bring participants from different studies together in a single analysis to investigate whether brain swelling after ICH affects outcome.

Lastly, Nesh will use all the information she's gathered to plan a large clinical trial to test the most promising inflammation-modifying drugs that she's identified. Because of the challenges of recruiting participants to clinical trials on ICH, Nesh plans for this to be a specific type of trial called a multi-arm, multi-stage adaptive platform trial. This type of trial involves testing multiple different drugs at the same time, reviewing the findings regularly, and adapting the trial in response to the findings. The drugs with the most promising outcomes stay in the trial, while those with the least promising outcomes are dropped.

Nesh says, "A platform study is a more efficient trial design which allows researchers to test multiple possible treatments at the same time rather than setting up separate studies to test each one. This means that we can work out whether a treatment works more quickly."

What is the benefit of this research?

Within the lifetime of Nesh's lectureship, her work should give us a much better understanding of how the brain responds to ICH, whether brain swelling does affect outcome after ICH, and what existing drugs could help modify that response.

If she's successful in identifying possible treatments, Nesh's planned clinical trial could also begin within the next five years. In the longer term, one or more drugs that can modify brain inflammation could be available to people who have ICH, boosting their chances of survival and of returning to independence.

What PSP priorities does this research link to?

From 2019 to 2021, we worked with the James Lind Alliance on the Stroke Priority Setting Partnership (PSP). During the PSP process, we collaborated with people with lived experience of stroke and stroke professionals to find out what they thought were the top priorities in stroke research. From this, we identified the top ten priorities in two areas: prevention, diagnosis and short-term care, and rehabilitation and long-term care.

Now, when researchers apply to us for funding, we require that their work addresses at least one of these priorities, or a priority from the Childhood Neurological Disabilities PSP Top 10 as it relates to childhood stroke.

Nesh’s project addresses the following priorities from the Stroke PSP:

• Prevention and acute 3: Benefits and risks of treatments for bleeding strokes
• Prevention and acute 4: Benefits and risks of new therapies for stroke
• Prevention and acute 10: Effects of other health conditions and characteristics on stroke

Meet the researcher

Nesh is an honorary senior clinical lecturer at the University of Edinburgh and a consultant neurologist for NHS Lothian. Previously, she was co-lead on the Stroke Association-funded NICHE project, during which she laid some of the groundwork for this lectureship.

Nesh says, "I got into stroke research in 2010, when I was a trainee neurologist. I wanted to be able to make a difference to patients who are having a stroke, having seen through my clinical work the awful impact that stroke has on patients and their loved ones. Over my last 20 years as a doctor, I have spoken to many stroke patients and their relatives so understand the need to find better treatments, especially for bleeding stroke which lags behind ischaemic stroke. This lectureship gives me the opportunity to work with others towards finding effective treatments."

Nesh will be working alongside multiple other researchers during her lectureship, including several other current and former recipients of Stroke Association Lectureships such as Professor Emily Sena, Dr Adrian Parry-Jones, and Dr Grant Mair. She also hopes to continue to build a team of ICH researchers, including supervising other people to take their first steps into research as they work with her on this project.