Neonatal White Matter Injury Trial (WRAP)

Preterm white matter injury (WMI) is the most common type of brain injury in premature infants and is associated with adverse neurological outcomes, including motor and cognitive disability and seizures. Preterm WMI involves an arrest of differentiation in the oligodendroglial cell lineage and a failure of normal developmental myelination. No therapies exist that directly promote brain repair and myelination or can be given at the time that preterm WMI has been identified and is likely most amenable to treatment. The lack of available treatments inherently limits the possibility for functional recovery in affected infants. Clemastine is an antihistamine and antimuscarinic agent that was identified in a high-throughput screen of FDA-approved compounds that significantly promote myelination in vitro. Clemastine was subsequently shown to promote myelination and improve functional recovery in multiple animal models of WMI, including preterm WMI, and induces remyelination in adult patients with multiple sclerosis. Clemastine is therefore an ideal potential candidate treatment for preterm WMI. The investigators will be conducting a Phase I/Ib open label dose-escalation and dose expansion study to test the safety and pharmacokinetics of oral clemastine treatment in neonates with preterm WMI.