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.
In this project, Dr Moon was working on the development of a new therapy to improve recovery in stroke patients by enhancing the ability of the brain and spinal cord to ‘rewire’ itself.
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 the single biggest cause of severe disability.
The number of deaths from stroke is less than half what it was 30 years ago. This is due in part to a reduction in the incidence of strokes, but also to a greater awareness of symptoms - meaning that help is sought sooner - combined with 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 1.4 million stroke survivors in the UK today.
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 also common.
In addition to the huge personal impact on the lives of stroke survivors, the impact on society is enormous. The economic burden of stroke in the UK is estimated at £9 billion a year - including health and social care costs, informal care, productivity losses and benefit payments. Two-thirds of working age survivors are unable to return to work.
Improving stroke recovery to enable survivors to live independent, productive lives is a therefore a key goal.
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 to 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.
With our funding, Dr Moon and colleagues set out to improve movement after stroke by developing a new therapy to enhance neuroplasticity in stroke patients. They had already developed a gene therapy to increase the body's production of a growth factor called Neurotrophin-3 (NT3), which is required for development of some spinal circuits involved in movement, and which can improve walking in rats after stroke and brainstem injury.
The team's aim was to develop a gene therapy that would stimulate production of NT3 in skeletal muscle only when an antibiotic called doxycycline is given, so that production could be turned down or off. Their new therapy was combined with rehabilitation, using their so-called 'RatBots', which provide automated, in-cage delivery of sugar pellets to promote rehabilitation of grasping in the rats.
Unfortunately, however, even with a large dose of doxycycline, it did not prove possible to get a high enough level of NT3 for benefit in the rats.
Whilst the disappointing results have paused this work for now, the research has usefully advanced knowledge by providing additional proof of principle that a transferred human gene ('transgene') can be controlled by doxycycline, and showing that the transgene can be switched on and off. The team's therapy used an 'Adeno-associated viral vector' to deliver the gene therapy; these types of vector are already used in various medicines that have been approved for use worldwide for other neurological disorders, and ongoing development of regulatable gene therapies could be transformative.
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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Find out about our other research in this area:
