Epidemiology, Pre-clinical & Neuroprotection

Preclinical trials will be conducted to test promising neuroprotectants. Trials will be translated to phase II/III trials in infants at high risk of cerebral palsy.

We are testing a range of novel neuroprotectants, cells and rehabilitations: (i) Melatonin (an antioxidant with anti-inflammatory and anti-apoptotic effects); (ii) Inflammasomes (enhance secretion of extracellular vesicles and modulation of their protein cargo with neuro-modulatory and neuro-repair effects) and (iii) cell therapies. Substantial preclinical evidence now exists to support the conduct of human trials evaluating stem cell therapy for perinatal brain injury. For children with CP, stem cells appeared to induce short-term improvements in gross motor skills, despite acknowledged trial limitations. Further research, in particular RCTs, using rigorous methodologies will be conducted. Different types of cells have been proposed, including amnion epithelial cells (AECs); mesenchymal stromal/stem cells (MSCs); umbilical cord blood (UCB), and neural progenitor/neural stem cells (NSCs). These cell types have different mechanisms of action and routes of administration that must be considered when designing clinical trials. AEC, MSC and UCB cells have anti-inflammatory and trophic properties, and therefore theoretically will be of most benefit during the primary phase (first 6hrs) of neuroinflammation, if neuroprotection and repair is sought. If administered in the chronic tertiary phase, smaller gains may still be possible via trophic effects and the emerging evidence that inflammation persists into the tertiary phase of injury. Contrastingly, in addition to anti-inflammatory and tropic properties, NSCs may also act via regenerative mechanisms i.e. cell replacement properties, thus making them a better therapeutic target for tertiary stage injury.

Current Projects in this theme:

     

    Past Projects: