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:
- Understanding the epidemiology of CP
- Optimising neurodevelopment for fetal growth restriction (FGR)
- Targeting the inflammasome: the key to curing cerebral palsy?
- MSCs for inflammation-induced preterm brain injury in the fetal sheep
- Stem cell therapy treatment for neonatal hypoxic-ischemic encephalopathy (HIE)
- Postnatal therapeutics for improving neurodevelopmental outcomes in IUGR
- Targeting the blood brain barrier (BBB) for the treatment of neuborn brain injury
Past Projects:
- Birth Asphyxia Brain Injury: The Babi Study
- Cord blood stem cells for cerebral palsy.
- Ganaxolone (GNX): A new treatment for neonatal seizures.
- Stem cell treatment for neonatal hypoxic-ischaemic encephalopathy
- Contribution of systemic inflammatory response to brain injury in growth restricted newborns
- Protecting growth restricted newborn brains by reducing inflammation
- A pre-clinical trial of early blood transfusion for improving cerebral oxygen delivery in very preterm neonates
- Blood biomarkers of brain injury following hypoxia-ischaemia in the neonate
- Novel approaches to protecting the newborn brain
- Carbon dioxide as a treatment for seizures in the newborn