Glaucoma Gene Therapy

Background

30% of all glaucoma patients do not have any therapy options. Current therapies are focused on symptom relief (i.e. reduction of eye pressure) rather than disease correction Medication compliance is complicated, and adherence among glaucoma patients is poor (<35%). UMass Chan researchers have created a treatment that actually treats and corrects Glaucoma with the AAV2-sFasL gene therapy.

Technology Overview

AAV2-sFasL gene therapy prevents axon degeneration and retinal ganglion cell (RGC) death in chronic and inducible models of glaucoma. These effects occur independent of intraocular pressure (IOP). Importantly, the AAV2-sFasL treatment works even after disease onset.

In three independent mouse models of glaucoma, mice that express only mFasL exhibit accelerated RGC death. In contrast, Fas or FasL deficiency, or administration of soluble FasL protects RGCs from cell death. In the healthy eye, FasL is constitutively cleaved to sFasL; whereas during glaucoma, FasL is expressed as a membrane bound protein (mFasL).

A one-time intraocular injection of AAV2 sFasL gene therapy provides complete and sustained neuroprotection in DBA/2J and acute microbead induced models of glaucoma, despite continuing elevated IOP.

Stage of Development: Preclinical Testing (April 2024)

Published manuscript:

Gregory MS, Hackett CG, Abernathy EF, Lee KS, Saff RR, Hohlbaum AM, Moody KS, Hobson MW, Jones A, Kolovou P, Karray S, Giani A, John SW, Chen DF, Marshak-Rothstein A, Ksander BR. Opposing roles for membrane bound and soluble Fas ligand in glaucoma-associated retinal ganglion cell death. PLoS One. 2011 Mar 29;6(3):e17659. doi: 10.1371/journal.pone.0017659. PMID: 21479271; PMCID: PMC3066205.

Benefits

A potential treatment and long term correction for glaucoma.

Applications

Glaucoma treatment.

Opportunity

Licensee or commercial partner to further testing and commercialization of this technology.