Active projects
Glioblastoma – a specific type of brain cancer
Glioblastoma is a devastating condition, with only 5% of patients surviving beyond 5 years. It is the most common primary brain cancer in adults, with around 2,500 cases diagnosed each year in the UK. A grade 4 tumour, glioblastoma 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. These treatments prolong survival but are not curative. Only a quarter of patients survive more than a year from diagnosis.
- We are working with Brain Research UK and this has led to a successful application for a Studentship in Glioblastoma by research student, Febe Ferro, at the University of Dundee who is looking into the fundamental mechanisms leading to the formation of glioblastoma cells. Enzymes are proteins that help speed up metabolism or chemical reactions in our bodies. They build some substances and break others down. All living things have enzymes and they are naturally produced in our bodies. Febe is investigating a specific enzyme that is greatly elevated in stage IV brain cancer. It has been shown in experimental settings that absence of this enzyme in the tumours radically extends the survival of mice bearing brain cancer. This needs to be explored in much more detail to see if it could be a potential target and whether it could make the brain cancer much more amenable to chemotherapy and immunotherapy.
- Medicines that boost our immune systems can be effective for some cancers but there is a barrier in brain blood vessels that prevents their use. We are supporting work at the University of Edinburgh into mechanisms that might make immunotherapy more effective for glioblastoma. The team led by Professor Alison Hulme are exploring ways round this.
Motor Neurone Disease
We have three projects focusing on motor neurone disease (MND).
With support from MND Scotland, funding is being provided
to
- the University of Glasgow to explore the potential value of high field MRI in getting a better handle on the condition
- and at the University of St Andrews and
- the University of Dundee the basic mechanisms are being explored in tissue samples.
Prevention of stroke
There are two types of stroke. The first is when clots in the blood supply prevent nutrients getting to brain tissue. The other is when leakages from blood vessels lead to internal bleeding. This is the cause of around 13% of all strokes.
Along with TENOVUS Scotland, we are supporting work at the University of Strathclyde into possible ways of reducing the likelihood of bleeds in the brain – known as hemorrhagic stroke. The work is led by Professor Hilary Carswell. The team will be exploring the potential of materials derived from parasitic worms. These materials have been shown to have the properties needed to stop the leakage of blood.
We provide full or part funding for studentships and projects that help researchers to get preliminary data to improve their bids to larger funding bodies. The trustees of the Foundation were, therefore, delighted when our £9.6K award for a stroke study led to a £250K grant. Professor Keith Muir at the Queen Elizabeth University Hospital in Glasgow lead the study.
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.
Stroke, head injury and Alzheimer’s Disease
Researcher Dr Kristin Flegal, came to Glasgow University from the University of California. She worked with Dr Will McGeown at Strathclyde University. Together they developed self-help strategies to limit the effects of memory loss in patients with stroke and head injury.
The technique explored in this project is called adaptive training. This is where the level of difficulty of training tasks increases throughout the training period. We liked this study as it aimed to give the subjects some ownership of their condition rather than just relying on drugs.
Final Report by Drs Flegal and McGeown – November 2020
Cognitive impairment in Parkinson’s Disease is multifactorial: A neuropsychological study
Final Report by Callum Smith – June 2020
Schizophrenia
We supported Dr Rajeev Krishnadas and his colleagues. They are using advanced medical imaging techniques to study information circuits in the brain in patients presenting with schizophrenia. One of the challenges facing them is to study the patients before they get antipsychotic drug treatment as that could affect the pattern of brain activity.
Migraine Project
Migraine is an often-disabling neurological disorder affecting around 1 billion people worldwide. It is triggered by the calcitonin gene related peptide (CGRP). This is a chemical produced in nerves in the face. In this project, a team is 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.
The prototype new migraine medicines work in animal models but are quickly broken down by enzymes in the blood. 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. This hides the peptide from the enzymes that break it down.
Recent studies show that the modifications have not hindered the biological effect for treating migraine. This is a very exciting development that it is hoped to improve on further over the coming months, thanks to The Neuroscience Foundation funding.
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 us.
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 known that glioblastoma cells spread from the original tumour site. 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.
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. The award helped them to set up a European network to investigate why patients often develop unexpected complications after head injuries. There are centres in the following locations –
* Glasgow
* Edinburgh
* Birmingham
* Liverpool
* Oxford
* Nottingham
* Newcastle
* Barcelona
* Leuven (Belgium)
* Iasi (Romania)
* Bristol,
* London (St George’s)
* Manchester Riga (Latvia)
* Bucharest (Romania)
As a result of the initial study that we funded, further grant income was secured. 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.
Acute stroke – Assessment and therapy combined
An original award of ~£10,000 from NSF has so far led to a further £1.6M grant income. There are also 5 full peer reviewed publications and a spinout company – Aurum Biosciences – has been formed. Aurum Biosciences 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. To do this a material called ABL101 will be administered to patients who will have an MRI scan.
As well as enabling regions of low metabolism to be identified, ABL101 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
Research In 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.
Brain Tumour Project
The Neurosciences Foundation raised £150,000 to support the pioneering work of Professor Moira Brown. Prof Brown 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. This led to the formation of Crusade Laboratories Ltd.
