Sghrt Polypeptide Inhibition for Cardiomyocyte Regeneration
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Solution Overview
Problem
Current treatments for heart failure are inadequate and primarily focused on cumulative add-on therapies, with limited regenerative capacity due to the inability of adult cardiomyocytes to divide effectively.
Innovation Solution
A polypeptide encoded by Sghrt, which is a mitochondrial micropeptide, is identified and used to assess heart function by determining its expression levels in subjects. The polypeptide is also used to develop methods for treating impaired heart function by inhibiting its expression or using inhibitors targeting the polypeptide.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If cumulative add-on therapy is used for heart failure treatment, then treatment coverage is improved, but therapeutic effectiveness deteriorates due to limited regenerative capacity
Solution Approach 1:
The patent introduces an intermediary substance (e.g., growth factors, cytokines, or small molecules) that mediates between the existing therapeutic regimen and the cardiomyocytes to stimulate proliferation. This intermediary acts as a bridge to activate endogenous regenerative mechanisms without directly replacing the cumulative therapy approach.
Solution Approach 2:
The patent employs parameter changes by modifying cellular state parameters through pharmacological intervention. Specifically, it changes the proliferation state of cardiomyocytes from quiescent to active by altering key regulatory parameters such as cell cycle progression markers, metabolic state, or signaling pathway activation levels, thereby enabling regeneration while maintaining treatment versatility.
2Productivity
If adult cardiomyocytes are targeted for proliferation, then regenerative capacity is improved, but control over cell division deteriorates due to inability to adequately undergo cell division
Solution Approach 1:
The patent implements feedback control mechanisms where the proliferation stimulus is regulated by monitoring cellular responses. The system adjusts the level or duration of proliferative signaling based on feedback from cell cycle markers, preventing uncontrolled division while maximizing regenerative output. This creates a self-regulating system that balances productivity and control.
Solution Approach 2:
The patent employs periodic application of proliferative stimuli rather than continuous exposure. By delivering treatment in controlled cycles or pulses, it allows cardiomyocytes to progress through cell division in regulated phases, maintaining control over the process while achieving cumulative regenerative effects over time.
3Reliability
If novel peptidic targets are identified to drive cardiomyocyte proliferation, then therapeutic potential is improved, but development time deteriorates as drivers remain elusive
Solution Approach 1:
The patent utilizes self-service by leveraging the heart's own endogenous signaling molecules and pathways that naturally regulate cardiomyocyte proliferation. Instead of discovering entirely new external targets, it identifies and modulates existing self-regulatory mechanisms within the cardiac system, significantly reducing development time while maintaining high therapeutic potential.
Solution Approach 2:
The patent identifies peptidic targets that serve multiple functions in cardiac physiology, allowing a single therapeutic intervention to address both regeneration and maintenance of normal cardiac function. This multi-functionality accelerates development by reducing the need for separate targets for different therapeutic goals.
Data Source
AI summary
The invention relates to an isolated polypeptide encoded by Sghrt and related uses. In addition, methods of assessing a heart function, treating impaired heart function by inhibiting Sghrt, identifying a potential drug for treating impaired heart function, and dedifferentiating and/or proliferating a heart cell by inhibiting Sghrt are claimed.