Splicing-Modulating Pharmaceutical Composition for Genetic Disease
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Solution Overview
Problem
Current treatments for genetic diseases caused by aberrant splicing events, such as Fabry disease, rely on symptomatic therapies, and there is a need for curative therapeutics with novel strategies.
Innovation Solution
A pharmaceutical composition containing a compound that suppresses splicing abnormalities, enhancing exon recognition or inhibiting aberrant splicing to restore normal splicing patterns, thereby treating or preventing genetic diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If symptomatic therapy is used for Fabry disease, then disease symptoms can be managed, but the underlying splicing abnormality remains untreated and disease progression continues
Solution Approach 1:
The patent applies preliminary action by developing splicing modulating compounds that can prevent aberrant splicing before it occurs. The compounds are designed to bind to pre-mRNA and redirect splicing factors, thereby preventing the formation of abnormal splice variants that would lead to disease. This proactive approach addresses the underlying genetic defect rather than merely managing symptoms after they manifest.
Solution Approach 2:
The patent uses splicing modulating compounds as intermediaries between the genetic defect and the splicing machinery. These small molecule compounds act as mediators that bind to specific sequences in pre-mRNA (such as exonic or intronic splicing enhancers/silencers) and recruit or block splicing factors, thereby correcting aberrant splicing patterns without requiring gene replacement or complex cellular reprogramming.
2Quantity of substance
If enzyme replacement therapy is used for Fabry disease, then enzyme deficiency can be compensated, but the splicing mutation causing the deficiency is not corrected
Solution Approach 1:
The patent applies the taking out principle by extracting and correcting the specific splicing defect without replacing the entire enzyme or gene. The splicing modulating compounds specifically target and correct the aberrant splicing event caused by the mutation, separating the splicing correction function from the enzyme replacement function. This allows the cell's own machinery to produce the correct enzyme variant.
Solution Approach 2:
The patent enables self-service by allowing the patient's own cells to produce functional enzyme through corrected splicing. Rather than continuously supplying external enzyme, the splicing modulating compounds enable the endogenous gene to be properly expressed, making the cellular system self-sufficient for producing the correct enzyme variant.
3Object-affected harmful factors
If conventional therapies are used for genetic diseases with splicing mutations, then symptom relief can be achieved, but curative treatment remains unavailable
Solution Approach 1:
The patent applies parameter changes by modifying the splicing parameters of the pre-mRNA through small molecule compounds. The compounds alter the binding affinity of splicing factors to specific sequences, change the conformation of pre-mRNA, or modify the kinetics of splicing reactions. These parameter changes redirect the splicing outcome from abnormal to normal, providing a curative mechanism rather than just symptomatic relief.
Data Source
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Figure 3A~3B
AI summary
A pharmaceutical composition for genetic diseases caused by an aberrant splicing regulation is provided. Provided are a pharmaceutical composition for preventing, ameliorating, suppressing progression of, and/or treating the genetic diseases caused by an aberrant splicing regulation, the pharmaceutical composition containing, as an active ingredient, a compound capable of suppressing an aberrant splicing regulation that contributes to the development or progression of genetic diseases caused by an aberrant splicing regulation, and a method for preventing, ameliorating, suppressing progression of, and/or treating the genetic diseases using a compound capable of suppressing an aberrant splicing regulation that contributes to the development or progression of genetic diseases caused by an aberrant splicing regulation.