Clinical Research; Research Networks; Laboratory Based Research


Click on each link below to find out more:

Behavioural research (led by Prof Steve Dunnett)
Clinical neuroscience (led by Prof Anne Rosser)
Genetics research group/stemcell theraphy (led by Dr Nick Allen)
Molecular research (led by Dr Lesley Jones)

Behavioural research (led by Prof Steve Dunnett)

The Brain Repair Group research programmes
Advances in our understanding of mechanisms of cell death, plasticity and regeneration in the central nervous system offer new opportunities for remediation and repair in several of the most distressing neurodegenerative diseases of adulthood, in particular Parkinson's and Huntington's disease. In the Brain Repair Group, we are seeking to develop new strategies for therapy based on a multidisciplinary approach in several converging problems:
Models of disease
We require valid models of disease in order to evaluate novel treatments. We compare neurochemical, excitotoxic, metabolic and transgenic strategies, both in vitro and in vivo, for their accuracy in reproducing the specific patterns of neuropathology and mechanisms of cell death observed in Huntington's disease, and for their reliability in providing stable models within which to compare different treatments strategies.
Neural transplantation
Improving the yield of surviving cells has turned out to be a key factor in viability of neural transplantation in Parkinson's disease, and this is likely to be of equal importance when applied to Huntington's disease. We are working to refine the methods for neural transplantation into the nervous system to yield optimal survival and growth of the implanted cells. Critical factors involve identification, dissection and handling of embryonic donor cells, and the surgical implantation protocols that maximise accuracy of placement and minimise trauma both to the host and to the implants. Alternative
cells for therapy
The successful clinical trials of transplantation have to date all used embryonic donor tissues. However, whereas surgeries based on using human embryonic tissues can provide a 'proof of principle' the long term development
and wider availability of neural transplantation is critically dependent on the identification of more readily available alternative sources of cells. We are actively exploring expanded populations of human embryonic, fetal and germ-line derived stem cells, xenografts, and genetically manipulated cells and cell lines for their ability to provide safer, more readily available, quality-assured alternatives to primary embryonic neurones for transplantation.
Neuroprotection
A complementary approach to cell transplantation (which involves replacing cells once already lost) is to protect damaged or traumatised neurones of the host brain from the assault of injury or disease. A wide number of compounds
have been identified which have the potential to block processes of cell death and to promote regrowth of damaged cells, including growth factors, antiapoptotic agents, antioxidants and transcription factors. However a common problem for their use is that they don't get into the brain when injected or ingested peripherally. We are developing ways to deliver neuroprotective agents into precise sites in the brain both by engineering cells for transplantation
('ex vivo gene therapy') and by using viral vectors for direct intracerebral delivery ('in vivo gene therapy').
Neurological assessment
The viability of each strategy needs to be evaluated in functional models of the disease. This requires development of behavioural and other functional models of assessment that are both sensitive to the neuroanatomical systems under investigation and relevant to the specific diseases targeted. A key component of our programme is to refine methods of functional analysis according to these dual goals, with a particular focus on objective operant tests of motor and cognitive function.
Clinical trials
We co-ordinate the first multicentre UK clinical trial to assess feasibility and safety of human fetal tissue transplantation in early- to moderate-stage Huntington's disease. Part of the surgical trial  set-up involved the development and validation of the core assessment protocols for intracerebral transplantation (CAPIT-HD), that has provided a major input into the more recent design of European Huntington’s disease Network project: REGISTRY.