Human Stem Cell-Derived RGCs for Optic Nerve Regeneration

Neurofibromatosis type 1 (NF1) is the most common genetic condition in which individuals carrying the mutation are predisposed to develop a variety of types of tumors. Approximately 20% of children with NF1 mutations will develop tumors of the nerve that carries visual information from the eye to the brain, so called optic pathway gliomas (OPGs). NF1-OPGs can cause permanent vision loss ranging from a mild decline in visual acuity to complete blindness.

Vision loss from NF1-associated optic pathway gliomas ultimately results from damage to and loss of the retinal ganglion cells (RGCs), the nerve cells of the eye that carry visual information to the brain. Since mammalian RGCs do not regenerate, for those patients who have already suffered significant RGC cell death and associated vision loss, we need to develop technology to replace a patient’s lost RGCs with human stem cell derived RGCs.

We have already developed methodology to create RGCs from stem cells generated from a small skin biopsy or blood sample. As part of VRI, we will optimize this methodology and better characterize the resulting RGCs at the single cell level. We will also perform screens to identify molecules and genes that can help the new RGCs, after transplantation into the eye, find their targets in the brain. Although there is still a long road ahead, based on exciting recent work in the field, there is now real hope that the Exogenous RGC Replacement will be successful and help lead the way to restoring vision to those suffering from NF1 OPGs and other forms of optic nerve disease.

Investigators

Donald Zack, MD, PhD

The Johns Hopkins University

Donald Zack, MD, PhD

The Johns Hopkins University

Current Stage

Discovery

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