Dr Lawrence Moon, King’s College London
Testing a new therapy to promote recovery from stroke
Dr Lawrence Moon was awarded a Brain Research UK project grant in September 2017 to take forward the development of a new therapy to enhance recovery after stroke.
Better awareness and improved treatment have both contributed to a reduction in mortality from stroke. But many survivors are left with disabilities that limit their ability to live productive, independent lives. Improving stroke recovery is therefore a key clinical and scientific goal.
Dr Moon is developing a new therapy that aims to improve recovery in stroke patients by enhancing the ability of the brain and spinal cord to ‘rewire’ itself.
Following rigorous assessment as part of our competitive project grant round, this project was selected for funding under our ‘acquired brain damage’ theme. The members of our Scientific Advisory Panel felt that the project would make an important contribution to knowledge in an important area, with high unmet need.
Members of the Panel were impressed by the clever idea, which is supported by extensive preliminary data and maps out a clear pathway for translation to human trial.
A stroke occurs when blood supply to part of the brain is cut off. This starves the brain of oxygen, with devastating consequences. Stroke is the fourth single largest cause of death in the UK, and a leading cause of disability.
The number of deaths from stroke is going down. This is partly due to a reduction in the incidence of strokes, but also to a greater awareness of symptoms - meaning that help is sought sooner - and the availability of better emergency treatments.
The lower mortality rates mean that more people are surviving stroke than ever before and it is estimated that there are 1.2 million stroke survivors in the UK today.
Almost two thirds of stroke survivors leave hospital with a disability. The range of disabilities associated with stroke includes limb weakness, impaired mobility, visual impairments and problems with speech, balance and co-ordination. Fatigue, depression and anxiety are common amongst survivors.
Improving stroke recovery to enable stroke survivors to live independent, productive lives is a key goal.
Read more: Stroke
Enhancing recovery after stroke
The brain and spinal cord have a remarkable ability to ‘rewire’ themselves after injury. This rewiring process – called neuroplasticity - can take place over many months and years and helps explain how, with the help of rehabilitation, people can recover functions that were initially lost as a result of injury.
Rehabilitation can be slow and frustrating, however, and often stretches the resources of healthcare systems, which struggle to deliver enough rehabilitation in the timeframe required.
Considerable research effort has been devoted to finding ways to enhance neuroplasticity in order to facilitate faster, more complete recovery from brain injury.
Dr Moon and colleagues are developing a new therapy designed to enhance neuroplasticity in stroke patients. They have already shown how their therapy improves walking in adult and elderly rats after stroke and brainstem injury and they are now refining the approach. The therapy involves delivery of a growth factor (Neurotrophin-3) that helps rewire brain and spinal circuits after stroke.
They are carrying out essential testing in rats, as a precursor to moving to human clinical trial. They have developed so-called “RatBots”, which provide automated, in-cage delivery of sugar pellets to promote rehabilitation of grasping in the rats.
They will assess the consequences of treatment in rats using methods that could be applied to humans in a clinical trial.
The team’s longer-term objective is to run a Phase I trial of this therapy in human patients after stroke, and this project will pave the way for such a trial.
The impact of stroke is enormous – at both an individual and a societal level.
Improving stroke recovery is a crucial clinical and scientific goal but our healthcare systems struggle to deliver enough rehabilitation in the timeframe required.
A treatment that can enhance recovery could deliver huge benefits for hundreds of thousands of stroke survivors in the UK alone. And whilst this project focuses on stroke patients, the treatment will also have applicability to those affected by other forms of neurological injury.
This is a proof-of-concept experiment, supported by extensive preliminary data, using rats to test a novel therapy for stroke.
It has clinical promise because it is based on a treatment that is already known to be safe in humans, and the administration of which is feasible in a timeframe that is relevant for stroke.
If the therapy, combined with intensive rehabilitation, leads to a large enough benefit in rats, the team will seek funding to take the therapy forward to human trial.
“Overall, this is a project with clear aims and whose completion could be very significant in helping to treat a significant brain problem,” external reviewer.
Related research projects
Acquired brain and spinal cord injury - which includes stroke - is one of our current priority research areas, 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.
In addition to Dr Moon's project, we are funding the following other projects under this theme:
- Professor Nick Ward, UCL Institute of Neurology: Investigating spontaneous early recovery after stroke
- Professor Simone Di Giovanni, Imperial College London: Regeneration and recovery following spinal cord injury
- Professor Sven Bestmann, UCL Institute of Neurology: When and how should we apply brain stimulation to help recovery after stroke?
- Franziska Mueller, Imperial College London: Restoring function after spinal cord injury (PhD studentship)