CRYM Inhibitory Therapeutic Agent for Sarcopenia

Solution Overview

Problem

Current treatments for muscle weakness symptoms and metabolic diseases, such as sarcopenia, do not effectively address the regulation of muscle plasticity and metabolic properties, particularly in relation to thyroid hormone action.

Innovation Solution

A therapeutic agent targeting μ-crystallin (CRYM) using CRYM inhibitory substances like antisense nucleic acids, RNAi-inducing nucleic acids, or low molecular weight compounds to inhibit CRYM activity, thereby regulating thyroid hormone action and enhancing muscle metabolism and strength.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Use of energy by moving object

If CRYM is overexpressed in skeletal muscle, then thyroid hormone action is enhanced, but muscle weakness and metabolic dysfunction occur

Engineering Contradiction:

Core Design Contradiction:

Use of energy by moving objectVSStrength

Solution Approach 1:

The patent applies inversion by administering CRYM inhibitory substances to reduce CRYM protein levels, thereby reversing the pathological overexpression state. This approach converts the harmful effect of enhanced thyroid hormone action into a beneficial therapeutic effect by restoring normal muscle function and strength while improving metabolic parameters.

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent changes the concentration parameter of CRYM protein in skeletal muscle from overexpressed to reduced levels through pharmacological inhibition. This parameter change restores the balance between thyroid hormone action and muscle function, simultaneously improving metabolism and muscle strength.

Inventive Principle:

Principle #35Parameter changes

2Strength

If CRYM activity is inhibited, then muscle strength is improved, but thyroid hormone action is reduced

Engineering Contradiction:

Core Design Contradiction:

StrengthVSUse of energy by moving object

Solution Approach 1:

The patent optimizes the inhibition level of CRYM to achieve a therapeutic window where muscle strength is improved while maintaining adequate thyroid hormone action for metabolism. The dosing regimen and inhibitory substance selection are tuned to achieve this balance.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent applies partial action by using CRYM inhibitory substances that reduce but do not completely eliminate CRYM activity. This partial inhibition is sufficient to improve muscle strength while preserving enough CRYM function to maintain normal thyroid hormone action and metabolism.

Inventive Principle:

Principle #16Partial or excessive action

3Strength

If conventional treatments are used for sarcopenia, then general muscle weakness is addressed, but specific regulation of muscle plasticity and metabolic properties is not achieved

Engineering Contradiction:

Core Design Contradiction:

StrengthVSAdaptability or versatility

Solution Approach 1:

The patent uses CRYM as a molecular intermediary to connect thyroid hormone signaling with muscle plasticity and metabolic regulation. By targeting CRYM specifically, the treatment achieves precise regulation of muscle properties through this intermediary, rather than using broad-acting conventional therapies.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent extracts and targets the specific molecular mechanism (CRYM-mediated thyroid hormone action) that regulates muscle plasticity and metabolism, separating it from general muscle weakness treatment. This allows for targeted therapy that specifically addresses the regulatory defects in sarcopenia.

Inventive Principle:

Principle #2Taking out (Extraction)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The therapeutic agent significantly suppresses muscle weakness and improves metabolism by upregulating thyroid hormone action, particularly in type II fast muscle fibers, making it effective for treating sarcopenia and disorders of carbohydrate metabolism.

Implementation Method 1

RNAi-inducing nucleic acids against CRYM

Methodology Applied

Scientific EffectRNA interference:

Implementation Method 2

antisense nucleic acid against CRYM

Methodology Applied

Scientific EffectAntisense nucleic acid inhibition:

Implementation Method 3

μ-crystallin (CRYM) was first identified in the kangaroo eye lens and has been characterized as an NADPH-dependent cytosolic triiodothyronine (T3)-binding protein, regulating 'triiodothyronine (T3)' transportation from cytoplasm to the nucleus

Methodology Applied

Scientific EffectThyroid hormone binding:

Implementation Method 4

Thyroid hormone has important roles in an extensive range of physiological functions, such as regulation of normal development, cellular proliferation and differentiation, thermogenesis, homeostasis, and metabolism

Methodology Applied

Scientific EffectThyroid hormone action:

Data Source

PatentUS10913949B2Therapeutic agent for sarcopenia and metabolic diseases

Publication Date: 2021.02.09

AI summary

The present invention provides a therapeutic agent for a muscle weakness symptom (sarcopenia) or a metabolic disease, containing a μ-crystallin (CRYM) inhibitory substance as an active ingredient. The inhibitory substance is selected from the group consisting of an antisense nucleic acid against CRYM, an RNAi-inducing nucleic acid against CRYM and a ribozyme against CRYM, expression vectors of these, an antagonist antibody against CRYM, and a low molecular weight compound that inhibits activity of CRYM.