Neuroprotection and Neuroenhancement in Ophthalmology

ReNetX is developing Nogo Receptor decoy as an orthogonal approach to maintaining and recovering visual function independent of stress (i.e., pressure, abnormal vascularization, inflammation, etc.). In the context of glaucoma, Nogo Receptor decoy is being developed to treat patients that continue to experience loss of vision despite treatment with current standard of care for lowering ocular pressure. The target profile is to stop or reduce the decline in visual function with neuroenhancement upon initiation of treatment due to repair of damaged synaptic connections. ​

Nogo Receptor Decoy in Ophthalmology

Nogo Receptor 1 (NgR1) is expressed broadly in retinal ganglion cells (RGCs) and targeting NgR1 pathway with Nogo Receptor decoy has been shown in preclinical models to improve RGC survival under conditions of stress. Nogo Receptor decoy also has the potential to repair damaged synaptic connections in the eye leading to some recovery of function (neuroenhancement) in the context of progressive synaptic dysfunction that has been found to precede RGC death.

Mechanism of Action

Preclinical studies  have shown that the Nogo Receptor decoy mechanism promotes survival of neurons, axonal growth, and synaptogenesis. In the eye, administration of Nogo Receptor decoy promoted survival of retinal ganglion cells under conditions of stress (i.e., increased ocular pressure) and following direct damage to the optic nerve. Axonal growth was enhanced following optic nerve injury in animals treated with Nogo Receptor decoy.​

In preclinical models of neurologic injury, Nogo Receptor decoy has been shown to promote axonal growth and recovery of function.

The first clinical trial with Nogo Receptor decoy (AXER-204) was conducted in patients with chronic cervical spinal cord injury.  Topline results indicate safety, pharmacokinetics and efficacy signals paving the way for further neurology trials.