Development of a novel therapeutic for treatment of white matter injury in premature infants

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Project Summary One in ten babies are born premature in the United States and are at risk of white matter injury (WMI). WMI is the most common neonatal brain injury leading to poor neurologic outcomes in premature infants, including cerebral palsy, intellectual disability, epilepsy, and blindness. Currently, there are no treatment options available for WMI. Developing novel therapeutics for use in neonates is particularly challenging due to appropriate concerns for safety in this extremely vulnerable population. As such, therapeutic development must have safety in the forefront during preclinical development. In addition, most WMI in neonates is undetectable for months following the injury. Therefore, the ideal therapeutic strategy would be safe enough to administer to infants that fall into high-risk categories following complications of preterm birth. Tellus Therapeutics has identified a novel myelinating compound present in human breastmilk with potential to treat neonatal WMI and a high likelihood for safety. We have strong preliminary data indicating that this compound induces oligodendrogenesis in vitro and in vivo, and rescues perinatal WMI in a mouse model, stimulating myelination and preventing motor deficits in mice that survive perinatal sepsis. Systemic delivery of this compound to the premature infant is complicated by hydrophobicity and the inability of this population to take medication or food by mouth, and the restricted fluid volumes tolerated by premature infants. In this Phase I SBIR project, we are pursuing an innovative approach to drug delivery in preterm neonates, with the goal of identifying a formulation to be used in IND-enabling studies and to serve as a prototype upon which to base the formulation for clinical studies. Toward this goal, Aim 1 will be focused on developing a novel, lipid emulsion formulation for intravenous delivery and Aim 2 will perform pharmacokinetic (PK) and central nervous system exposure analyses in neonatal pigs with the goal of identifying a formulation that can be used in IND-enabling studies in Phase II.