Small Molecules for Satellite Cell Proliferation

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Solution Overview

Problem

There is a need for compositions and methods to enhance satellite cell proliferation, which is crucial for muscle growth and repair, particularly in conditions like Duchenne muscular dystrophy and sarcopenia where satellite cells are depleted or inefficient, affecting muscle recovery and growth.

Innovation Solution

The method involves contacting satellite cells with compounds such as kinase inhibitors, G protein coupled receptor modulators, epigenic modifiers, histone deacetylase modulators, hedgehog signaling pathway modulators, neuropeptides, dopamine receptor modulators, serotonin receptor modulators, histamine receptor modulators, adenosine receptor agonists, ionophores, and ion channel modulators to increase proliferation without affecting differentiation potential.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If satellite cells are depleted or their function is adversely affected by aging or disease, then muscle growth and repair capacity deteriorate, but conventional treatments do not effectively expand the endogenous satellite cell population

Engineering Contradiction:
Improvesatellite cell numberVSAvoidsatellite cell function
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent employs small molecules that modify biochemical parameters within satellite cells to induce proliferation. Specifically, compounds are used to alter cellular signaling pathways, epigenetic modifications, and metabolic states, transforming quiescent satellite cells into proliferating myoblasts without compromising their myogenic differentiation potential.

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent utilizes small molecule compounds as intermediaries to mediate the transition from quiescent satellite cells to proliferating myoblasts. These compounds act as chemical messengers that bind to specific cellular targets, triggering intracellular signaling cascades that promote cell cycle entry and proliferation while preserving differentiation capacity.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If satellite cells proliferate extensively to expand the stem cell pool, then muscle repair capacity improves, but the cells may lose their differentiation potential and myogenic capacity

Engineering Contradiction:
Improvesatellite cell proliferation rateVSAvoiddifferentiation potential
Core Design Contradiction:
ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent applies partial action by using controlled doses of small molecules that stimulate proliferation to a sufficient but not excessive degree. The treatment regimen is designed to achieve the necessary expansion of satellite cell numbers while stopping before the cells lose their differentiation potential, maintaining a balance between proliferation and myogenic capacity.

Inventive Principle:
Principle #16Partial or excessive action

Solution Approach 2:

The patent employs periodic treatment protocols where small molecules are administered in controlled cycles. This periodic exposure allows satellite cells to proliferate during treatment phases while maintaining the ability to differentiate during intermission phases, preventing permanent loss of myogenic potential through repeated alternating stimulation and rest periods.

Inventive Principle:
Principle #19Periodic action

Data Source

PatentUS20240366627A1Small molecules for mouse satellite cell proliferation
Publication Date: 2024.11.07 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US20240366627A1 patent drawing
  • US20240366627A1 patent drawing
  • US20240366627A1 patent drawing

AI summary

The invention provides methods for inducing, enhancing or increasing satellite cell proliferation, and an assay for screening for a candidate compound for inducing, enhancing or increasing satellite cell proliferation. Also provided are methods for repairing or regenerating a damaged muscle tissue of a subject.