Development of Therapeutic Strategies for NF1-Associated Optic Pathway Glioma
Abstract
Approximately 15 percent-20 percent of individuals with neurofibromatosis type 1 (NF1) develop low-grade glioma, mainly along the optic pathway (optic pathway glioma or NF1-OPG). Almost all NF1-OPGs arise in children younger than 7 years of age, suggesting that a complete loss of NF1 due to the "second-hit" must occur in developing neural stem and/or progenitor cells during acritical window of optic nerve development. However, the phenotypic consequences of Nf1 loss on glial cell lineages in the developing optic nerve remain unknown. The overall objective of this proposal is to understand the disease mechanism that transforms NF1-OPGs from a neurodevelopmental defect into a blinding disease and, more importantly, to design preventive or early interventional treatments that can effectively prevent or reverse visual deterioration. Two specific aims are proposed. Aim 1: To determine cellular targets and molecular mechanisms of the developmental defect(s) caused by Nf1 loss that induces progressive OPGs. Aim 2: To develop preventive and early interventional therapies that improve visual impairment in a preclinical NF1-OPG model. This project will develop a novel concept about the pathogenesis of NF1-OPG - the severity of developmental defects in glial lineages of the developing optic nerve determines the fate of OPGs, and will provide insights on how developmental defects in the optic nerve determine the behavior of OPGs - from asymptomatic to progressive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2021
- Accession Number
- AD1165177
Entities
People
- Yuan Zhu