Thrasher Research Fund - Medical research grants to improve the lives of children

Project Details

Early Career

Status: Funded - Closed

Caffeine mediated augmentation of mitochondrial p27 as a novel neurotherapeutic for neonatal HIE

May Chen, MD


BACKGROUND: Neonatal hypoxic‐ischemic encephalopathy (HIE) is brain damage in infants that causes significant mortality and morbidity worldwide despite the use of therapeutic hypothermia as the current standard of clinical care. Supplemental therapies for HIE are urgently needed. Drugs that act on mitochondria may reduce brain damage because mitochondrial dysfunctional is ubiquitously involved in neuronal cell death. Caffeine is now known to target the mitochondria through pleiotropic mechanisms of action. GAP: There are no published caffeine studies in large animal HI models to our knowledge. Furthermore, the mechanisms driving caffeine neuroprotection are unclear and possibly separate from its effect on adenosine receptors. HYPOTHESIS: We hypothesize that caffeine confers neuroprotection after HI through mitochondrial protection and p27 signaling. METHODS: We will use whole body HI to mimic clinical HIE. Full‐term, neonatal swine (2‐3 days old) will be randomized to HI or sham procedure and also to caffeine with a single or multi‐dose regimen or vehicle. RESULTS: Pending. IMPACT: This project will enable us to collect essential preliminary data in identifying a new treatment to prevent neurological disabilities in HIE, expand the clinical relevance of p27 as a therapeutic target beyond childhood cancer by pioneering novel aspects of neurobiology related to p27, and potentially establish the basis for a clinical trial using caffeine as a supplemental treatment to hypothermia for HIE. Website Link: https://www.jennifer‐k‐lee‐

Supervising Institution:
Johns Hopkins University School of Medicine

Jennifer Lee-Summers

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