MYLIP_PRINT: exploiting the role of MYLIP positive pericytes

Pericytes malfunction after spinal cord injury (SCI) are known to lead to blood spinal cord barrier (BSCB) dysfunction and decrease blood flow, enhancing the secondary damage. Targeting pericytes to promote spinal cord repair, in particular their endogenous nature, might promote a reduction in the neuroinflammation and improve barrier integrity. Recently we have identified a new vascular protein, MYLIP (myosin regulatory light chain interacting protein), which expression is injury-induced in pericytes surrounding the lesion area in the
mouse contusion model of SCI. MYLIP expression is observed in pericytes that are attached and detached from blood vessels, also suggesting a role of MYLIP in fibrosis formation. This expression localizes with more predominance on the caudal side of the injury, a place where subpopulations of pericytes have already been described to mediate constriction mechanisms that decrease spinal blood flow and, if identified, can contribute to a decrease in hypoxia and therefore reduce inflammation, improve myelination and regrowth.
We believe that MYLIP positive pericytes constitute a new subpopulation of pericytes that are important not only for scar formation but also for the perpetuation of hypoxia and neuroinflammation. In this project we aim
to better describe and characterize this particular population and demonstrate that targeting MYLIP expression, through antisense oligonucleotides therapy, will promote a better functional outcome through the reduction of inflammation, which will demonstrate its future translational value. This project is a perfect combination of an innovative breakthrough idea with an experienced and talented team and has great potential to contribute for the discovery of new therapeutic strategies for SCI and therefore have a socioeconomic impact within the field and in the quality of life of these patients.