Neuroscience research activity at Barts and The London lies predominantly within the Blizard Institute of Cell and Molecular Science but is an important strength across the School.
Research in neuroscience is focused on translational work in the fields of traumatic injury, degenerative disorders and neuro-oncology, building on both internal investment and external funding.
The Blizard Institute of Cell and Molecular Science, returned in Hospital Subjects, was ranked in the 2008 Research Assessment Exercise joint 1st with Cambridge and Edinburgh in terms of 3* and 4* outputs and was joint 7th overall out of 28, ahead of Manchester, Newcastle and Southampton.
Neurology Clinical Outcomes Unit
A major objective is to strengthen the links between academic and clinical activity in Neuroscience and, to this end, the establishment of a Neurology Clinical Outcomes Unit is planned, along with the formation of an acute spinal injury unit with close links to the Helicopter Emergency Medical Service and trauma work within Barts and The London NHS Trust.
To deliver this agenda, the group has appointed a new head, Professor Gavin Giovannoni, a world-leader in neuroimmunology.
Neuroscience research focuses on three interrelated topics:
- The role of primary sensory neurons and effects of peripheral nerve injury
- Traumatic and degenerative disorders of the central nervous system
- Molecular mechanisms of development and central nervous system tumorigenesis - a new theme and one which reflects the importance of cancer both for the School and for Barts and The London NHS Trust.
Primary sensory neurons
Work here focuses on the fundamental role played by neurotrophic factors and cytokines in regulating adult dorsal root ganglion (DRG) cells, the importance of such factors in pain states, and strategies to promote peripheral nerve regeneration.
Professor John Priestley’s group was the first to establish that nociceptive DRG neurons comprise two main subpopulations which differ in their growth factor dependence and expression of neuropeptides.
This work is continuing, with further study of the properties of nociceptive DRG neurons, their expression of key transduction molecules and ion channels, and their response to injury.
Professor Priestley’s group has shown that novel silks developed by Oxford Biomaterials can support neural regeneration. This work is now funded by a £250,000 grant from Kinetique, awarded to establish a start-up company (Neurotex) and develop silk-based conduits for peripheral nerve repair.
The Centre’s pre-clinical studies are complemented by clinical studies on orofacial neuropathic pain, on perioperative pain relief and on arthritis.
Traumatic and degenerative central nervous system injury
The Centre has an established reputation for work on degenerative disorders including motoneurone disease and traumatic injury to the spinal cord. This has recently been further strengthened with the establishment of a neuroimmunology group with a focus on multiple sclerosis (MS) and basal ganglia autoimmune diseases.
Research ranges from cell and molecular studies in vitro, through in vivo rodent models, to clinical trials. This translational focus is facilitated by the presence of a full-time trials coordinator. Ongoing studies include root avulsion injury, molecular strategies to promote regeneration and hence link closely with the peripheral nerve work reviewed above. Studies on spinal cord injury include the use of fibronectin implants to fill cystic cavities and support axonal regeneration, strategies to promote regeneration after ventral root avulsion injury, and use of omega-3 polyunsaturated fatty acids (PUFAs) as neuroprotective agents. A phase 1 safety study of PUFA treatment in spinal cord injury is underway, as is a pilot clinical study in Alzheimer’s disease.
Motor neuron disease
Key recent achievements related to motor neuron disease include the linkage of axonal transport defects to motor neuron loss in dynein mutations and gene array analysis of common mechanisms underlying motor neuron disease and cell death following spinal cord injury.
The neuroimmunology group leads the field in studies of endocannabinoids in MS and the possible therapeutic use of cannabinoids in MS.
They have also highlighted the role of anti basal ganglia autoantibodies in movement disorders, and are developing novel treatments for MS based on induction of immune tolerance.
Development and neuro-oncology
The molecular events that determine gene transcription and cellular differentiation are being studied, both in normal development and in tumour formation. Major themes currently under investigation include: the role of chromatin and nuclear architecture in transcription (Sheer); genetic defects associated with glioblastoma multiforme (Sheer); the molecular events that control cerebellar granule cell development and their contribution to the pathogenesis of medulloblastoma (Marino); and the role of neural stem cells and self renewal mechanisms in the ontogenesis of brain tumours (Marino). The latter studies provide a strong link with stem cell work in other research centres at Barts and The London.