Stem cell treatment for neonatal hypoxic ischemic encephalopathy
Grant Type: Project Grant
Chief investigators: Colditz P, Khosrotehrani K, Bjorkman T, Patel J, Wixey J
Aim: To undertake a systematic pre-clinical study to identify an effective stem cell treatment for neonatal hypoxic ischaemic encephalopathy (HIE).
Background: Neonatal HIE is a major global cause of infant mortality and morbidity. In Australia, moderate or severe neonatal HIE occurs in 2–6/1000 live births with rates up to 5-fold higher in low income countries. There is a high burden of death and lifelong disability; about 25% die and about 25% of those who survive develop permanent motor, cognitive and sensory neurodevelopmental disabilities. HIE is the cause of 15–28% of cerebral palsy and a major lifelong disease burden in terms of emotional, family and economic costs. Hypothermia treatment has resulted in improved outcomes for newborns with HIE, however 1 in 4 of these babies still die and 1 in 4 survivors will have cerebral palsy. There is a compelling need for additional therapies to reduce the high rate of death and disability in HIE. Stem cell therapy is a key candidate and one we are in an ideal position to progress.
Hypothesis: Stem cell treatment will provide neuroprotection in the pre-clinical model of neonatal HIE
Methods: In a pre-clinical piglet model of HIE, to optimise stem cell treatment by:
• incorporating hypothermia therapy
• using placentally-derived, high-dose, sorted stem cells
• studying the effect of adjuvant therapy, erythropoietin
Impact: We will use our established piglet model with the incorporation of hypothermia treatment which is standard care in human neonates with HIE. We will establish the neuroprotective efficacy of the stem cell treatment and also any additive protective effect of the adjuvant erythropoietin by measurement of functional and structural brain outcomes. The use of human cells has the merit of being immediately relevant to use in clinical trials. Our established track record and clinical networks will enable effective translation of this study to a definitive RCT in babies.
