SMN Protein Stabilizer and SMN2 Enhancer Combination

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Solution Overview

Problem

Current therapeutic strategies for spinal muscular atrophy (SMA) are inadequate in effectively increasing full-length SMN protein levels, stabilizing the protein, and modulating splicing patterns to treat the disease effectively.

Innovation Solution

Development of compounds and compositions that include SMN protein stabilizers and SMN2 transcription enhancers, such as those with specific chemical formulas, to increase full-length SMN protein production by stabilizing SMN2 mRNA and protein, and administering these compounds in combination with other SMA treatments.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If current therapeutic strategies are used to elevate full length SMN protein levels, then some increase in SMN protein may be achieved, but the increase is insufficient to effectively treat SMA

Engineering Contradiction:

Improvefull length SMN protein levelsVSAvoidtreatment effectiveness

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent combines multiple therapeutic agents with different mechanisms of action into a single composition. Specifically, it merges splicing modulators (which increase exon 7 inclusion), SMN protein stabilizers (which prevent protein degradation), and transcription enhancers (which increase SMN2 gene expression) into one synergistic formulation, thereby achieving sufficient SMN protein elevation to effectively treat SMA

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The patent creates a composite therapeutic composition containing multiple active ingredients with complementary functions. This composite approach integrates agents that work at different levels of the SMN production pathway (transcription, splicing, and protein stability), producing a synergistic effect that exceeds the sum of individual agent effects

Inventive Principle:

Principle #40Composite materials

2Adaptability or versatility

If single mechanism therapies are used to modulate splicing or stabilize protein, then specific mechanisms can be targeted, but comprehensive SMN protein elevation and stabilization is not achieved

Engineering Contradiction:

Improvemechanism targeting capabilityVSAvoidSMN protein stability

Core Design Contradiction:

Adaptability or versatilityVSStability of the object's composition

Solution Approach 1:

The patent merges agents targeting different mechanisms (splicing modulation, protein stabilization, transcription enhancement) into one composition, allowing simultaneous targeting of multiple steps in the SMN production pathway while achieving comprehensive protein elevation and stabilization

Inventive Principle:

Principle #5Merging (Combining)

Data Source

PatentUS10420753B2Combination therapies for treatment of spinal muscular atrophy

Publication Date: 2019.09.24 INDIANA UNIVERSITY RESEARCH & TECHNOLOGY CORP

AI summary

Disclosed herein are compositions and methods for treatment of spinal muscular atrophy (SMA). In certain embodiments, compounds are provided that increase full-length survival of motor neuron (SMN) protein production by an SMN2 gene.