Babies born preterm are particularly susceptible to brain injury as a consequence of hypoxic or hypoxic-ischemic events either in utero, during delivery, or in the early days of neonatal intensive care. With modern neonatal intensive care, survival of these preterm babies has increased, but brain injury remains a significant concern. Currently, there are no suitable biomarkers of injury to aid early identification of babies at risk of brain injury and no really effective therapies to reduce injury.
Exosomes, small vesicles, are naturally capable of penetrating the blood brain barrier, and have the capacity to communicate with the microenvironment through transfer of proteins, miRNAs and other nucleic acids. Given they can traverse across the blood brain barrier to the plasma, profiling of their cargo may hold significant early diagnostic and prognostic value, and inform on emergent treatment response. Additionally, growing evidence is supportive of their intrinsic neuroprotective therapeutic activity, as well as being ideal candidates to deliver targeted therapeutic molecules of choice through modifications to enhance delivery. Currently, we are undertaking both preclinical and clinical studies to provide critical new information on the usefulness of exosome-derived miRNAs in the diagnosis of preterm brain injury. Furthermore, using our clinically relevant fetal sheep model of preterm brain we are investigating the regenerative and immunomodulatory capacities of human fetal neural stem cell-derived exosomes.