Investigation of PEGylated BA-210 for RGC neuroprotection

Project summary Inhibitors of Rho GTPase are neuroprotective for retinal ganglion cell (RGCs) and may be effective in treating eye diseases such as glaucoma. RGC death in glaucoma is associated with RGC axonal loss. Once neurons lose connections, normal circuitry is affected, and the loss of target-derived signals contributes to cell death. Such loss of signals may be dendritic or axonal, and prevention of RGC cell death would be improved by drugs that stimulate plasticity and/or prevent axonal die back. BA-210 is a Phase II investigational drug (in clinical trial for acute spinal cord injury) that has strong neuroprotective effects and also stimulates dendritic plasticity and axonal regeneration. We have strong preclinical data for neuroprotection of RGCs after intravitreal injection in rats after axotomy of the optic nerve and in a rat model of elevated intraocular pressure (IOP). To improve the pharmacodynamics and safety of BA-210 for use in ophthalmology, we will make PEGylated BA-210. We will determine