ALS Treatment Compounds Targeting SOD1 Aggregation and Misfolding
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Solution Overview
Problem
Current treatments for amyotrophic lateral sclerosis (ALS) are limited, particularly in addressing the aggregation and misfolding of superoxide dismutase 1 (SOD1) proteins, which are key contributors to the progression of the disease, and there is a lack of effective inhibitors targeting this mechanism.
Innovation Solution
Development of novel compounds, such as PRG-A-01 and PRG-A-04, which act as SOD1 aggregation and misfolding inhibitors, blocking the propagation of SOD1 proteins and reducing neuronal cell death by inhibiting WT-SOD1 aggregation and misfolding.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for ALS, then disease progression is addressed, but aggregation and misfolding of SOD1 proteins are not effectively inhibited
Solution Approach 1:
The patent introduces novel compounds (Formula 1 and Formula 2) as intermediary substances that specifically bind to and inhibit the aggregation and misfolding of SOD1 proteins. These compounds act as mediators between the harmful SOD1 aggregation process and the desired therapeutic outcome, blocking the propagation of misfolded proteins without directly affecting normal SOD1 function.
Solution Approach 2:
The patent modifies the chemical structure of SOD1-interacting compounds by changing molecular parameters such as the introduction of specific functional groups (carboxy, hydroxy, alkoxy substituents) and adjustment of molecular weight and binding affinity. These parameter changes enable the compounds to specifically target and inhibit SOD1 aggregation while maintaining safety and efficacy.
2Object-affected harmful factors
If SOD1 aggregation is inhibited, then neuronal cell death is reduced, but muscle weakness and movement disorders persist
Solution Approach 1:
The patent applies preliminary action by administering the novel compounds before significant neuronal cell death and muscle degradation occur. The compounds pre-inhibit SOD1 aggregation and misfolding processes, preventing the propagation of toxic protein aggregates through neural connections before they can cause widespread damage and functional loss.
Solution Approach 2:
The patent ensures continuity of useful action through sustained administration of the novel compounds that continuously inhibit SOD1 aggregation and misfolding. This continuous inhibition prevents the reformation of toxic protein aggregates and maintains neuronal health over time, addressing the progressive nature of ALS.
3Stability of the object's composition
If intraspinal nerves are maintained, then disease progression is slowed, but survival extension is limited
Solution Approach 1:
The patent incorporates feedback mechanisms through monitoring of disease progression markers and adjusting compound administration accordingly. The continuous inhibition of SOD1 aggregation creates a feedback loop where maintained intraspinal nerve function serves as an indicator of therapeutic efficacy, allowing for optimized treatment duration and dosage to maximize survival extension.
Data Source
AI summary
The present invention relates to a use of a novel compound, for preventing, improving or treating amyotrophic lateral sclerosis (ALS), wherein the present inventors have found that SOD1 aggregation is one of the important causes of ALS, and have proposed the possibility that WT-SOD1 aggregation, caused by suppressing the regulation of intracellular stress or TDP-43, may be a cause of sALS. In addition, the present inventors have discovered the novel compound PRG-A-01(SLC-B036) as a SOD1 aggregation and misfolding inhibitor.