Compositions and methods for treating misfolded protein ocular disorders
Inventors
Chen, Yuanyuan • Palczewski, Krzysztof
Assignees
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Publication Number
US-12678440-B2
Publication Date
2026-07-14
Expiration Date
Abstract
A method of treating an inherited ocular disorder associated with or caused by a misfolded ocular protein in a subject in need thereof includes administering to the subject a compound that promotes clearance of misfolded ocular protein.
Core Innovation
The invention relates to treating non-syndromic autosomal dominant retinitis pigmentosa (adRP) caused by misfolded ocular proteins. It provides a method that promotes clearance of misfolded ocular proteins in a subject by administering a therapeutically effective amount of a compound selected from a pharmaceutically acceptable salt, tautomer, or solvate, or combinations thereof.
In the disclosed approach, the subject has non-syndromic autosomal dominant retinitis pigmentosa associated with or caused by the misfolded ocular protein. The therapeutic intent is to accelerate degradation and clearance of the misfolded ocular protein in a way that improves ocular protein homeostasis while aiming to improve or preserve visual function and retinal structure.
The disclosure further ties the intended therapeutic outcomes to inhibition of photoreceptor cell death and improvement or preservation of retinal structure, including functional and structural readouts. It identifies misfolded opsin and misfolded rhodopsin with specified mutations, and reports preservation of photopic electroretinogram (ERG) response and outer nuclear layer (ONL) thickness.
Claims Coverage
The document provides two independent methods centered on administering a therapeutically effective amount of a selected compound to subjects with non-syndromic autosomal dominant retinitis pigmentosa associated with or caused by a misfolded ocular protein.
Administering a therapeutically effective amount to promote clearance of misfolded ocular proteins
A method of promoting clearance of misfolded ocular proteins in a subject comprises administering to the subject a therapeutically effective amount of a compound selected from a pharmaceutically acceptable salt, tautomer, or solvate, or combinations thereof, wherein the subject has non-syndromic autosomal dominant retinitis pigmentosa associated with or caused by the misfolded ocular protein.
Treating an inherited ocular disorder associated with or caused by a misfolded ocular protein
A method of treating an inherited ocular disorder associated with or caused by a misfolded ocular protein in a subject in need thereof comprises administering to the subject a therapeutically effective amount of a compound selected from a pharmaceutically acceptable salt, tautomer, or solvate, or combinations thereof, wherein the subject has a non-syndromic autosomal dominant retinitis pigmentosa associated with or caused by the misfolded ocular protein.
Misfolded opsin target
The misfolded ocular protein is a misfolded opsin.
Specific opsin mutations for the misfolded opsin
The mutation is at least one of P23H, C110Y, D190N, T17M, P347S, or P267L.
Therapeutically effective amount for degradation, homeostasis, and photoreceptor protection
A therapeutically effective amount intended to accelerate degradation of a misfolded ocular protein, improve ocular protein homeostasis, improve or preserve visual function and retinal structure, and/or inhibit photoreceptor cell death.
Photopic electroretinogram response as a visual function outcome
Improving or preserving visual function includes improving or preserving photopic electroretinogram (ERG) response.
Defined administration routes for the compound
The compound is administered via one or more routes selected from topical administration, systemic administration, intravitreal injection, and intraocular delivery.
Timing relative to retinitis pigmentosa staging
The timing of administration is selected such that it is early stage or mid stage.
Across the independent claims, the core requirement is administering a therapeutically effective amount of a selected compound form to a subject with non-syndromic autosomal dominant retinitis pigmentosa associated with or caused by a misfolded ocular protein. The claim set further focuses on particular misfolded ocular proteins, specified amino-acid mutations, intended acceleration of degradation and clearance with ocular protein homeostasis improvement, and preservation of visual and retinal structure outcomes.
Stated Advantages
Promotes clearance of misfolded ocular proteins.
Accelerates degradation of a misfolded ocular protein.
Improves ocular protein homeostasis.
Improves or preserves visual function.
Inhibits photoreceptor cell death.
Improves or preserves retinal structure.
Improves or preserves photopic electroretinogram (ERG) response.
Preserves outer nuclear layer (ONL) thickness.
Documented Applications
Treating non-syndromic autosomal dominant retinitis pigmentosa (adRP) associated with or caused by a misfolded ocular protein.
Using compounds identified from high-throughput screening to promote clearance of mutant-selective misfolded rhodopsin and to validate selected compounds across multiple cell models and an adRP mouse model.
Combination therapy context involving a rhodopsin chaperone and/or anti-retinal degeneration agents in conjunction with clearance-promoting compound administration.
Diagnostic/risk identification contexts described as symptomatic subjects and at risk subjects with a rhodopsin mutation.
Use in inherited ocular disorder treatment associated with or caused by a misfolded ocular protein.
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