Compositions and methods of treating age-related retinal dysfunction

Inventors: Jennings Luu (Oakland, CA); Krzysztof Palczewski (Oakland, CA)

Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

A61K31/437 A61K31/506 A61P27/02

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Quick Facts

Patent No.: US 12708616
App. No.: 18/006,176
Granted: Aug 18, 2026
Kind: B2

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Abstract

A method of treating and/or preventing age-related retinal dysfunction in a subject in need thereof includes administering to the subject a therapeutically effective amount of an agent that attenuates stress-induced chromatin remodeling associated with the age-related retinal dysfunction.

Claims (9)

1 . A method of treating age-related macular degeneration in a subject in need thereof, the method comprising:

administering to the subject therapeutically effective amounts of agents that attenuate stress-induced chromatin remodeling associated with age-related macular degeneration, wherein the agents comprise a histone deacetylase 11 (HDAC11) inhibitor and a suppressor of variegation 3-9 homolog 2 (SUV39H2) inhibitor.

2 . The method of claim 1 , wherein the age-related macular degeneration is associated with an increase in HDAC11 and SUV39H2 in the subject's eye.

3 . The method of claim 1 , wherein the age-related macular degeneration is associated with a decrease in H3K27ac in the retina and/or an increase in H3K9me in the retinal pigment epithelium and/or choroid of the subject and the agents are administered to the subject at amounts effective to increase H3K27ac in the retina and/or decrease in H3K9me in the retinal pigment epithelium and/or choroid of the subject.

4 . The method of claim 1 , wherein the age-related macular degeneration manifests as at least one of the following conditions: autofluorescent spots indicative of retinal pathology detected in the fundus by Scanning Laser Ophthalmoscopy (SLO), thinning of the photoreceptor containing outer nuclear layer (ONL) as characterized by Optical Coherence Tomography (OCT), a global reduction of chromatin accessibility as determined by an Assay for Transposase-Accessible Chromatin using Sequencing (ATAC-Seq), and photoreceptor degeneration.

5 . The method of claim 1 , wherein the HDAC11 inhibitor is a selective inhibitor of HDAC11 and/or the SUV39H2 inhibitor is a selective inhibitor of SUV39H2.

6 . The method of claim 1 , wherein the HDAC11 inhibitor is selected from SIS17, Quisinostat (JNJ-26481585), Fimepinostat (CUDC-907), Pracinostat (SB939), Mocetinostat (MGCD0103, MG0103), or Domatinostat (4SC-202).

7 . The method of claim 1 , wherein the SUV39H2 inhibitor is selected from OTS186935 or OTS193320.

8 . The method of claim 1 , wherein the agents are delivered to the subject by at least one of topical administration, systemic administration, intravitreal injection, and intraocular delivery.