Neuroprotective agent in sight?

March 15, 2010

A neuroprotective approach to the treatment of glaucoma is not imminent, but several promising approaches are under investigation.

Durham, NC-A neuroprotective approach to the treatment of glaucoma is not imminent, but several promising approaches are under investigation. Areas that hold the most possibility are targeting amyloid-beta, complement activation, and tumor necrosis factor (TNF)-alpha signaling, said Stuart J. McKinnon, MD, PhD.

"Will we have one in our lifetime? I hope so," he added. Dr. McKinnon reviewed several therapeutic strategies that have been successful using animal glaucoma models.

This finding suggests a possible relationship between the two diseases, Dr. McKinnon said. Altered metabolism of amyloid-beta and amyloid precursor protein (APP), which plays a central role in neuronal homeostasis, contributes to apoptosis of retinal ganglion cells (RGC) in glaucoma.

Two classes of drugs are FDA-approved to treat AD: acetylcholine esterase inhibitors (donepezil [Aricept, Pfizer/Eisai], rivastigmine [Exelon, Novartis] and galantamine [Razadyne, Ortho-McNeil-Janssen Pharmaceuticals]), and an N-methyl-D-aspartate receptor antagonist, memantine (Namenda, Forest Pharmaceuticals).

In a rat glaucoma model, galantamine was more neuroprotective than donepezil or memantine, Dr. McKinnon said, but memantine did not show any improvement in glaucoma in a large multicenter clinical trial.

Two anti-amyloid approaches that may be useful in the treatment of glaucoma are decreasing amyloid-beta production by secretase inhibition or interfering with amyloid-beta aggregation by using amyloid-beta vaccination. Another strategy that has demonstrated neuroprotection in a rat glaucoma model is the use of intravitreal antibodies to amyloid-beta, Congo red, and beta-secretase inhibitors, singly or in combination.