Retinal Disease Composition for All-Trans-Retinal Cytotoxicity
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Solution Overview
Problem
Current treatments for hereditary and age-related retinal diseases, particularly those caused by ABCA4 genetic mutations and age-related macular degeneration, are limited, with no effective therapeutic agents available for the early dry form, leading to progressive blindness.
Innovation Solution
A novel composition comprising compounds represented by General Formulas 1 to 5, which include substituents such as alkyl, cycloalkyl, aryl, and heteroaryl groups, is developed to inhibit cytotoxicity, cell aging, and intracellular reactive oxygen species, thereby preventing or treating retinal diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If only one therapeutic agent targeting RPE65 gene is used, then treatment is available for a very small number of patients, but most hereditary retinal diseases remain untreated leading to progressive blindness
Solution Approach 1:
The patent develops a series of compounds (General Formulas 1-5) that can treat multiple types of retinal diseases including ABCA4-associated diseases and age-related macular degeneration, making the therapy universally applicable to various retinal conditions rather than limited to a single disease mechanism
Solution Approach 2:
The patent modifies chemical parameters by developing compounds with specific structural features (substituents R1-R17 in General Formulas 1-5) to optimize the therapeutic effect while maintaining broad applicability across different retinal disease types
2Reliability
If no treatment is available for early dry form of macular degeneration, then progression to late atrophic form can be prevented, but patients remain blind due to lack of therapeutic intervention
Solution Approach 1:
The patent provides compounds that can be administered in the early dry form of macular degeneration to prevent progression before irreversible damage occurs, enabling early intervention that stops disease progression to the atrophic stage
Solution Approach 2:
The compounds work by preventing the formation and accumulation of A2E photooxidant before it causes significant retinal damage, thereby providing preliminary protection against the harmful effects that lead to vision loss
3Object-generated harmful factors
If all-trans-retinal accumulates in retinal epithelial cells, then it forms photooxidant A2E through oxidative mechanism, but this toxic substance causes cytotoxicity and cell death in photoreceptor cells
Solution Approach 1:
The patent compounds convert the harmful accumulation of all-trans-retinal and A2E photooxidant into a beneficial outcome by reducing cytotoxicity and photooxidation, transforming the toxic metabolic pathway into a safer state that protects photoreceptor cells
Solution Approach 2:
The compounds act as intermediaries that interfere with the oxidative mechanism converting all-trans-retinal to A2E, serving as a mediator that blocks the harmful transformation process and reduces the formation of toxic photooxidant
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds exhibit excellent cytoprotective effects against cytotoxicity, inhibit cell aging, and reduce intracellular reactive oxygen species, effectively treating and inhibiting the progression of hereditary and age-related macular degeneration.
Implementation Method 1
the compounds of the present invention not only have an excellent cytoprotective effect against cytotoxicity caused by all-trans-retinal and an inhibitory effect against cell aging caused by hydrogen peroxide, but can also effectively suppress the increase in intracellular reactive oxygen species caused by all-trans-retinal
Data Source
Figure 1(A)~1(B)
Figure 2
Figure 3(A)~3(C)
AI summary
The present specification discloses a novel composition for preventing or treating retinal diseases. In one aspect, compounds in the present invention are extremely effective in protecting cells against the cytotoxicity of all-trans-retinal, inhibiting cellular aging, and inhibiting intracellular reactive oxygen species, and thus can be used in therapeutic agents for retinal diseases such as hereditary macular degeneration and age-related macular degeneration.