Method for treatment of macular degeneration by modulating P2Y12 or P2X7 receptors

摘要

Provided is a method of treating or preventing age-related macular degeneration (AMD) in a patient subject to, or symptomatic of the disease, wherein the method comprises restoring normal lysosomal pH (pHL), or acidifying an abnormally elevated pHL, thus decreasing or preventing a damaging accumulation of lipofuscin or waste products in the retinal pigment epithelium (RPE) cells of the eye of the patient. Further, this method is achieved by modulating the action of the P2X7 and/or P2Y12 receptors of the RPE cells, specifically decreasing the acidity (pHL) of the RPE lysosomes by administering selected receptor antagonists affecting the action of the P2X7 and/or P2Y12 receptors of the RPE. Methods for selecting and quantifying the effectiveness of drugs to restore pHL and determine outer segment clearance rates is also provided using a high through-put screening protocol.

主权项

1. A method of treating age-related macular degeneration (AMD) in a patient subject to or symptomatic of age-related macular degeneration (AMD), the method comprising administering to a patient at least one P2X7 receptor antagonist selected from the group consisting of A438079, (3-[[5-(2,3-dichlorophenyl)-1H-tetrazol-1-yl]methy]pyridine hydrochloride salt, C13H9C12N5•HC1, BBG for ophthalmic use, C47H48N3NaO7S2,Acid blue 90, Coomassie® Brilliant Blue G, A740003(18/40 nM), AZ-10606120(19/1.4nM); AZ-1645373(6 nM human); KN-62(15 nM human), A-839977, A-847227, AZ-116453743, GSK314181A, AFC-5128, AZD-9056, CE-224535, AF-4025, EVT 401, MRS 2159, MRS2306 and MRS 2540, to inhibit P2X7 receptor activity, thereby acidifying lysosomal pH (pHL) in the retinal pigment epithelium (RPE) cell(s) of the patient's eyes.