Research at the Bradbury Lab
Research in the Bradbury lab tries to understand the basic biology of the injured spinal cord, to find out why the spinal cord cannot repair itself and to develop new therapies to enhance nerve fibre regeneration, neuroplasticity and tissue repair, with the ultimate goal of improving function and quality of life after spinal cord injury. Our research spans two main themes:
Translational research aimed at developing promising therapies to treat clinical spinal cord injury
- Targeting the glial scar and extracellular matrix
- Restoring upper limb function after spinal cord injury
Mechanistic research into understanding injury and repair processes at the molecular level:
- Spontaneous repair, remyelination and neuregulin signalling
- Proteomics/ novel targets and biomarkers/ drug discovery
Targeting glial scar and extracellular matrix
The Bradbury lab has pioneered the use of an enzyme therapy that breaks down inhibitory matrix associated with the glial scar that forms at the site of a spinal cord injury. In a wealth of studies we have demonstrated that in vivo treatment with the enzyme chondroitinaseABC could promote neuroplasticity, matrix remodeling and tissue repair, leading to significant improvements in limb function and axonal conduction in clinically relevant models of spinal cord injury. The most recent focus is uses a gene therapy approach to optimize delivery to the spinal cord. This work has shown great promise and, as part of the CHASE-IT (chondroitinase for injury therapy) Consortium we are currently developing and testing a regulated vector-based chondroitinase gene therapy for human use. For this project we collaborate with Professor Joost Verhaagen (Netherlands Institute for Neuroscience), Dr Liz Muir (University of Cambridge) and Professor Yanez Munoz (Royal Holloway).
Restoring upper limb function after spinal cord injury
We are developing novel combination treatments to restore useful arm and hand functions following cervical spinal cord injury. We are using neurophysiology (repeated electrical stimulation of key pathways involved in forelimb function) and physical rehabilitation (repetitive reaching and grasping movements) and combining these with therapies which promote neuroplasticity (e.g. chondroitinase) to enhance the function of surviving systems and maximise recovery of specific upper limb and hand functions. Recovery of hand function is one of the highest priorities for spinal injured patients. For this project we collaborate with scientists, clinicians and research physiotherapists and occupational therapists at the Spinal injury Unit at the Royal National and Orthopaedic Hospital, Stanmore: Dr Sarah Knight, Natalia Vasquez and Professor Michael Craggs.
Spontaneous repair, remyelination and neuregulin signalling
Despite the severe neurological consequences of SCI, in nearly all cases there is some degree of functional improvement after the initial trauma and, at the cellular level, there is some attempt by the spinal cord to mount a regenerative response, which includes nerve fibre sprouting, myelin repair and neurogenesis. Although this repair is limited, there is clearly an endogenous capacity for repair in the spinal cord. If we can understand the basic biology underlying these regenerative processes, we may then be able to modulate and enhance them and improve functional outcome after SCI. we have identified neuregulin-1 as an important mediator of endogenous repair after spinal cord injuyry and we are developing ways to modulate neuregulin-1 signalling to improve tissue repair and restore function after spinal cord injury. For this project we collaborate with Professor David Bennett (University of Oxford).
Proteomics/ novel targets and biomarkers/ drug discovery
Following a traumatic spinal cord injury there is a period of aggressive tissue remodelling, scarring and inflammation (the secondary injury) which leads to the chronic pathology that is refractory to repair and recovery. Despite the well-known pathological changes, we still know little about the mediators of these events. We are studying mechanisms of inflammatory activation and extracellular matrix remodelling after spinal cord injury using proteomics, transcriptomics and systems-wide bioinformatics, to identify novel bioactive mediators and identify potential neew drug targets to improve tissue pathology and functional repair after spinal cord injury.