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We provide full or part funding for studentships and projects.

Glioblastoma – The Daphne Merrills Studentship

Glioblastoma is the most common primary brain cancer in adults, with around 2,500 cases diagnosed each year in the UK. It is a grade 4 tumour, meaning that it grows and spreads quickly. The current treatment strategy includes surgery to involve as much tumour as possible, followed by radiotherapy and chemotherapy to target the remaining tumour. This prolongs survival but is not curative, and only a quarter of patients survive more than a year from diagnosis.

If we imagine the brain as a building, the walls of said building are cells, each with different functions and roles, and together they ensure the building remains upstanding. Their building blocks (or bricks, if you will) are the proteins that ensure these walls can function properly. When glioblastoma enters the picture, there is a rearrangement of these bricks – some disintegrate, others change shape, some move to entirely different locations – and consequently this affects various walls which negatively impact the overall stability of the entire building.

Within this project, they are proposing to study a protein, or brick if we follow the analogy above, called Fam20C, that has been shown to be remarkably elevated in glioma tumours. Once more using our building analogy, if Fam20C is a square brick and we know there are only supposed to be twenty of these, but suddenly there are a hundred, this affects all the other bricks around them and therefore, eventually, the building as a whole. Glioma tumours lacking Fam20C do not grow well in mouse brain; its absence significantly extends survival. This suggests that Fam20C is important for tumour growth, and that blocking its effects could be a way to inhibit growth. They will investigate Fam20C in more detail, to understand its effects on the different cell types that make up the tumour, and fully understand its role in glioblastoma growth and development. This could open the way to the development of therapies that target these processes, making the brain cancer more susceptible to chemotherapy and immunotherapy.

Acute stroke

The Neurosciences Foundation provides funds for small projects that help researchers to get preliminary data to improve their bids to larger funding bodies. We were therefore delighted when our £9.6K award for a stroke study lead by Professor Keith Muir at the Queen Elizabeth University Hospital in Glasgow led to a £250K grant. Some strokes are caused by a large clot from the heart blocking blood supply to the brain. Current practice is to attempt to remove the clot, but only if this can be done within 4.5 hours of onset of the stroke.  Prof Muir’s team are exploring whether this time window could be extended to 24 hours. Clearly, the sooner treatment is applied the better. ‘Time is brain’ should still be the slogan, but perhaps there could be some benefit for patients up to 24 hours. We eagerly await the results of the full study.

Prevention of stroke

There are two types of stroke; clots in the blood supply that prevent nutrients getting to brain tissue, and leakages from blood vessels that lead to internal bleeding. This studentship focusses on the second of these, which is the cause of around 13% of all strokes. The team will be exploring the potential of materials derived from parasitic worms that have been shown to have the properties needed to stop the leakage of blood. The team is led by Dr Hilary Carswell at the University of Strathclyde.

Schizophrenia

We are supporting Dr Rajeev Krishnadas and his colleagues who are using advanced medical imaging techniques to study information circuits in the brain in patients presenting with schizophrenia. One of the challenges that the researchers are facing is to study the patients before they get antipsychotic drug treatment as that could affect the pattern of brain activity. They are making good progress.

Stroke, head injury and Alzheimer’s Disease

The researchers are Dr Kristin Flegal who came to Glasgow University from the University of California and Dr Will McGeown at Strathclyde University. They are developing self-help strategies to limit the effects of memory loss in these patients. The technique being explored in this project is called adaptive training, where the level of difficulty of training tasks increases throughout the training period. We like this study as it aims to give the subjects some ownership of their condition rather than just relying on drugs.

Early detection of deterioration in children who have had a head injury

This project is led by consultant neurosurgeon Mr Roddy O’Kane and clinical scientist Dr Ian Piper. This award helped them to set up a European network to investigate why patients often develop unexpected complications after head injuries. The network has been established successfully and has Centres in Glasgow, Edinburgh, Birmingham, Liverpool, Oxford, Nottingham, Newcastle, Barcelona, Leuven (Belgium) and Iasi (Romania) plus Bristol, London (St George’s), Manchester, Riga in Latvia, and Bucharest in Romania. As a result of the initial study that we funded, further grant income was secured. In particular the researchers were awarded an EU Grant of 600K Euro’s from the EU ERA-NET-NEURON programme to undertake studies using the network infrastructure.

Updates on some of our projects

1) Brain Cancer.

Dr Sarah Derby, Dr Ross Carruthers, Dr Joanna Birch and Prof Anthony Chalmers have completed a project in brain cancer with the help of funding from the Neurosciences Foundation.

Cancer treatments are designed to kill tumour cells but the DNA damage repair mechanisms in the body interfere with this. This has led to the use of DNA damage repair inhibitors. ATR inhibitor (ATRi) is one such substance. It is knows that glioblastoma cells spread from the original tumour site, and this is one reason why it is such a difficult condition to treat. However, it had been postulated that ATRi might limit this spread. This series of experiments was designed to get a better understanding of this process.

They have succeeded in doing this and the results have been submitted for peer review to a high impact journal. The group are planning to take this work forward to clinical trials.

2) Acute stroke. Assessment and therapy combined.

The original award of ~£10,000 from NSF has so far led to a further £1.6M grant income, 5 full peer reviewed publications and formation of a spinout company – Aurum Biosciences. The company has raised over £3M from investors in the UK and USA. The project aims to establish methods of assessing tissue metabolism in regions of the brain after a stroke by administering a material called ABL101 to patients and then using MRI scanning. The ABL101 enables regions of low metabolism to be identified. However, there could well be a bonus, as it should also improve the delivery of oxygen to parts of the brain that are compromised. Techniques like this are called ‘theragnostics’ because of the potential for both diagnosis and therapy. Clinical trials are underway.Further information is available at http://www.aurumbiosciences.com

3) Cognitive impairment in Parkinson’s Disease is multifactorial: A neuropsychological study  

Click to read the Final Report by Callum Smith – June 2020

4) Memory training for stroke and head injury patients

Click to read the Final Report by Drs Flegal and McGeown – November 2020

5) Research In The Intensive Care Units

Funding from the Neurosciences Foundation enabled Dr Ian Piper to obtain preliminary data that helped to secure a €2.3M framework 7 grant from the European Union.

6) Brain Tumour Project

The Neurosciences Foundation raised £150,000 to support the pioneering work of Professor Moira Brown, who demonstrated that a modified version of the HSV virus that causes cold sores could selectively destroy rapidly dividing cancer cells and not normal brain cells.

7) Migraine Project

Migraine is an often-disabling neurological disorder affecting around 1 billion people worldwide. It is triggered by the CGRP neuropeptide, a chemical produced in nerves in the face. In this project, our team are designing synthetic versions of CGRP that can mimic the natural CGRP and block its action. This is known to stop a migraine attack or prevent it from starting. Our prototype new migraine medicines work in animal models but are quickly broken down by enzymes in the blood, so their effects are very short-lived. Adam Schofield (PhD student in the Coxon Lab) has so far managed to make changes to the synthetic peptide that have extended the half-life from 30 minutes to ~26 hours through a process called lipidation. Lipidation is a method in which the peptide reversibly binds to another protein within the blood and this hides the peptide from the enzymes that break it down. Recent studies show that our modifications have not hindered the biological effect for treating migraine. This is a very exciting development that we hope to improve on further over the coming months, thanks to The Neuroscience Foundation funding.