Federal Project Grant Award Summary

The Children's Hospital of Philadelphia Research Institute received a $489,500 Project Grant from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), with award effective May 1, 2026 through April 30, 2028. The grant funds fundamental and translational research aimed at understanding the role of BLOC1S1 (biogenesis of lysosomal organelles complex-1 subunit 1) in myelin development and addressing the mechanisms underlying BLOC1S1-related leukoencephalopathy (BLOC1S1-LE), a rare neurological disorder characterized by hypomyelination, epilepsy, and developmental delays.

The research deliverables include mechanistic studies utilizing conditional mouse models to investigate how BLOC1S1 depletion disrupts autophagy and oligodendrocyte differentiation; generation of patient-derived induced pluripotent stem cells (iPSCs) to replicate disease phenotypes in oligodendrocyte precursor cells and mature oligodendrocytes; assessment of myelin protein and cholesterol transport in BLOC1S1-deficient oligodendrocytes; and functional rescue experiments using lentiviral BLOC1S1 constructs. The project addresses critical knowledge gaps regarding lysosomal function and vesicle homeostasis in myelin formation, potentially advancing therapeutic approaches for this rare pediatric neurological condition.