Neuroprotection and optic nerve regeneration in a mouse NF1 OPG model

Neurofibromatosis type I (NF1) occurs in one out of 3,000 people worldwide and can cause non-cancerous tumor growth in the peripheral and central nervous systems. 15 –20% of people with NF1 develop optic pathway gliomas (OPGs) in the first 7 years of life due to an excessive proliferation of astrocytes (support cells of the nervous system) and the invasion of tumors with microglia (resident immune cells in the nervous system). Retinal ganglion cells (RGCs), the nerve cells that send visual information from the eye to the brain, are vulnerable to the effects of aberrant astrocytes and microglia, and undergo cell death in many patients with OPGs, resulting in an irretrievable loss of vision.

The objectives of this project are to prevent RGCs from dying in cases in which NF1-associated OPGs are diagnosed at an early stage of progression and enable remaining RGCs to regenerate connections back to the brain in cases in which OPGs are diagnosed at a more advanced stage and axons have atrophied. Several treatments that have proven to be successful in preserving injured RGCs and/or enabling RGCs to regenerate damaged nerve fibers in earlier studies from our lab and others will first be tested individually for beneficial or possible negative effects in a mouse model of NF1-associated OPG. Therapies that prove to be benign or beneficial will then be combined and tested in larger groups in early and later stages of OPG progression in mice. In more basic research, we will investigate how 3 newly discovered pathways that regulate RGC survival interact with each other to develop better treatments for OPGs. Finally, we will work with the cell replacement groups to develop methods to enable endogenous or exogenous stem cell-derived RGCs to extend nerve fibers that can convey visual information to the brain. Our overall goal is to devise therapies that can be moved into clinical practice to improve vision in NF1 patients with OPGs.

Current Stage


In Vivo Proof of Concept
IND Enabling
Clinical Trial Phase 1
Clinical Trial Phase 2
Clinical Trial Phase 3