Case study: Searching for a stroke wonder drug
The study of stroke is a recognised research strength of the University. Our Manchester Stroke Research Group promotes interdisciplinary research in all aspects of stroke, working with stroke survivors and their carers, the public, clinicians and service commissioners, as well as clinical and non-clinical scientists.
Stroke is a devastating condition that can affect people of all ages, causing death and long-term disability. Stroke is an increasing problem globally, especially in developing countries where people have adopted more sedentary western lifestyles, which make them more prone to an attack.
Yet, despite a long global search, there has been little success in finding a wonder drug that can protect the brain cells killed by the condition.
Professor Stuart Allan, Professor of Neuroscience at the University, says the majority of people have a stroke for a reason, such as high blood pressure, vascular disease or clogged arteries. He says that what has emerged from recent research is the importance of considering these risk factors, and how stroke impacts the whole body and not just the brain, in developing new treatments.
“One of the suggestions for why there have been so many drug failures in this field is that we are not really fully considering other factors beyond the brain,” he says.
At present, stroke victims can be given a clot-busting drug in the aftermath of a stroke but, crucially, this would not be given until a patient has had a brain scan at hospital. Also, even if receiving a brain scan in time, patients might not be suitable for the clot-busting treatment, if for example they have bleeding in the brain rather than a blood clot.
Professor Allan adds: “Part of the problem is that having a stroke is a very instant thing. The death of brain cells after the blood supply is reduced is rapid, so the time window to treat the condition is very short.
"What we need is a drug that can be administered straight away, so that victims don’t have to wait until the brain scan, and so that the damaging effects of stroke are treated immediately. Hopefully this would then mean that the patient doesn’t have to spend as much time in hospital, and will be able to recover as much of their function as possible.”
This could really open up the field for drug companies to start working on finding treatments for stroke again.Professor Stuart Allan / Professor of Neuroscience
Inflammation in the brain
Stroke research at Manchester is particularly focussed on the role that inflammation plays in stroke.
Our immune system helps us to fight off infection and to repair the body after an injury. For many years, people believed inflammatory responses had little to do with the brain; however, it is now clear that inflammatory responses can occur in the brain. Rather than being a good thing, this brain inflammation can be involved in diseases of the brain, including stroke.
Professor Allan and his collaborators are specifically trying to understand how it is that inflammation causes brain cells to die. By doing this, they can design treatments that can stop the inflammation and hence the brain cells from dying.
“If you have a stroke, the blood supply to the brain decreases and there is a very rapid inflammatory response which increases the levels of toxic proteins in the brain. It is all about how we block these proteins and slow down this process.”
He and his colleagues, particularly Professors Nancy Rothwell and Pippa Tyrrell, have been working on developing such a drug for many years - and, excitingly, it will soon enter Phase 3 clinical trials for a particular type of stroke where there is bleeding in the brain, subarachnoid haemorrhage.
Professor Allan says, if successful, this would be a game-changer. “This could really open up the field for drug companies to start working on finding treatments for stroke again,” he explains.
Studying animal brains
We are learning more and more from animal studies in terms of the way that the brain works and how it is affected by diseases such as stroke.Professor Stuart Allan / Professor of Neuroscience
To fully understand the complexity of stroke and other diseases, one has to study the whole organism, which is why research that involves animals is so crucial in finding a successful drug.
Mice or rats are induced with a stroke so that they directly mimic what happens to a human. Scientists can then assess the amount of brain damage that takes place. This can be done using brain scanners, in a similar way as to would be done in humans with stroke. They can also look at how the behaviour of the animals undergoing the stroke is affected, assessing movement as well as memory and general wellbeing.
In this way, researchers are able to learn more about how the stroke affects individual animals. By doing so, they can better understand the mechanisms by which brain cells die and how this impacts other cells and tissues in the body.
This then allows new treatments to be developed that can affect these mechanisms, reduce the death of brain cells and improve outcome.
By trialling the drug on mice and rats, researchers can also look at the impact of doses, how to give the drug, what time to give it, and how frequently it should be administered.
Professor Allan adds: “We are learning more and more from animal studies in terms of the way that the brain works and how it is affected by diseases such as stroke.”