Intracerebral haemorrhage (ICH) is a devastating type of stroke, occurring when blood leaks out from a burst blood vessel in the brain. It has a poor prognosis – more than 40 per cent of patients die within a month, and those who survive usually have poor recovery.
In this project, Dr Zahraa Al-Ahmady and colleagues are focusing on the damage caused by the sudden presence of iron in the brain, resulting from the leaked blood. There are no effective treatments to counteract this, and the team will test ways of administering iron chelating drugs directly to the site of the injury.
Following rigorous assessment as part of our competitive grant round, this project was recommended for its logical and interesting approach to an important problem, and its potential to generate important new knowledge towards improved treatment for ICH.
Intracerebral haemorrhage occurs when a blood vessel bursts in the brain, causing blood to leak out into the surrounding tissue. The causes of ICH include high blood pressure, malformation of blood vessels and head trauma.
Accounting for 10 to 15 per cent of all strokes, ICH has a poor prognosis – more than 40 per cent of patients die within one month, and those who survive usually have poor recovery.
Emergency treatment is needed to stop the bleed, relieving pressure on the brain and restoring normal blood flow to all parts of the brain. But further damage can unfold once the bleed has been stopped, caused by the sudden presence of iron in the brain, from the leaked blood.
The iron can cause delayed and irreversible damage to the brain in a process called ferroptosis. No specific medications currently exist to prevent or treat this effect.
Iron chelators are drugs that bind to iron and prevent its accumulation. They have previously been tried in haemorrhagic strokes but were not effective, possibly due to failure of the drug to reach the target area of the brain in sufficient concentration. This cannot be solved by simply increasing the dose, as this causes unwanted side effects. There is a need to develop new methods to ensure that the drugs can reach the area of the stroke in sufficient concentration to exert their intended effect, but without exposing the rest of the body to unwanted side effects.
In her previous research, Dr Al-Ahmady has shown that it is possible to target the affected part of the brain using tiny parcels called liposomes. In this project, the team plans to package the liposomes with the iron chelating drugs to see if they can get the drugs to the target area in higher concentration without exposing the rest of the body.
The team will use a mouse model that mimics human brain haemorrhage to compare the effect of the packaged vs unpackaged iron chelator. This will enable them to determine whether the new liposome technology is more efficient, and has the potential to reduce or prevent brain damage after haemorrhagic stroke.
This project addresses the important problem of ferroptosis in ICH and sets out to establish an effective delivery mechanism for iron chelating drugs. This would represent an important step towards the development of an effective treatment to combat ferroptosis, and so reduce the risk of brain damage following ICH.
“This is a really solid project in a very important area. The potential impact is very high.”
External reviewer
Dr Al-Ahmady is an early career researcher with a strong track record in drug delivery research.
She has assembled a strong multi-disciplinary team across Nottingham Trent University and the University of Manchester, bringing essential skills and experience to deliver on every aspect of the proposed research and ensure its clinical relevance.
“The applicant is a very promising new investigator, the background and pilot data indicate an excellent understanding of the field, the clinical translation issues and the literature supporting both ferroptosis and ICH in general. The support team is excellent as well and the environment is highly conducive to success of the project.”
External reviewer
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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