Meninges as an overlooked pharmacological target for Globoid Cell Leukodystrophy

Globoid cell Leukodystrophy Disease (GLD) is a severe neurodegenerative life-threatening disease genetic disease that manifests early in life with rapid progression. There is no cure for GLD. Treatment options are still very poor. In this Project, the researchers will approach GLD pathogenesis and therapy from an entirely new angle. They will study GLD neurodegeneration and therapy by changing the focus from the nervous cells to the non-parenchymal brain cells. In particular, they will study the involvement of meninges in GLD pathogenesis and progression. Meninges are highly heterogeneous tissue with trophic, immune and neurogenic properties. Recently, Dr. Bifari has identified neural progenitor cell population in meninges that migrate to the cortex and differentiate into functional and integrated cortical neurons. In this project, the team will assess GLD-induced activation of meninges and meningeal neural progenitors. In addition, the team will exploit meninges as effective site for GALC gene transfer in GLD. Transduced meningeal cells may provide GLAC secretion to the brain (cross-correction) and GALC-transduced meningeal neural progenitors can migrate to the brain and differentiate into GALC-overexpressing cortical neurons.