Enolase 1 Muscle Delivery for Glucose Normalization

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Solution Overview

Problem

Current treatments for diabetes, particularly type 2 diabetes, are inadequate in reversing vascular and organ damages and are associated with debilitating side effects, while existing therapies for managing blood glucose levels are insufficient in maintaining normoglycemia.

Innovation Solution

Administration of enolase 1 (Eno1) or its fragments to muscle cells, either alone or complexed with muscle-targeting moieties and dendrimers, to enhance glucose uptake and insulin sensitivity, thereby normalizing blood glucose levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current diabetes treatments are used, then blood glucose levels can be managed, but vascular and organ damages are not reversed and debilitating side effects occur

Engineering Contradiction:

Improveeffectiveness in reversing vascular and organ damagesVSAvoiddebilitating side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the molecular parameter by using enolase 1 protein instead of conventional diabetes medications. Enolase 1 is administered at specific concentrations (e.g., 0.1-100 μg/kg body weight) to achieve glucose homeostasis without the harmful side effects of current treatments, directly addressing the contradiction between effectiveness and safety

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses recombinant human enolase 1 protein that replicates the function of endogenous enolase 1 in glycolysis. This copied protein restores normal glucose metabolism pathways, enabling reversal of vascular and organ damages while avoiding the side effects of synthetic diabetes medications

Inventive Principle:

Principle #26Copying

2Reliability

If insulin is administered to treat type 1 diabetes, then glucose metabolism is regulated, but the short serum half-life prevents maintenance of normoglycemia

Engineering Contradiction:

Improvemaintenance of normoglycemiaVSAvoidserum half-life of insulin

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent introduces enolase 1 protein as an intermediary substance that acts on peripheral tissues to enhance glucose uptake. Unlike insulin that requires continuous administration due to short half-life, enolase 1 provides sustained action by directly facilitating glucose metabolism pathways, thereby maintaining normoglycemia longer

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent replaces the hormonal mechanism of insulin (which has short half-life and requires continuous regulation) with a direct enzymatic mechanism. Enolase 1 protein substitutes for insulin's role in glucose regulation but through a different molecular pathway that provides more sustained action and better maintenance of normoglycemia

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Reliability

If lifestyle changes are adopted for type 2 diabetes, then some glucose control is achieved, but vascular and organ damages are not reversed

Engineering Contradiction:

Improvereversal of vascular and organ damagesVSAvoidinsufficiency of lifestyle changes

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent introduces enolase 1 protein as a therapeutic intermediary that directly acts on peripheral tissues to reverse vascular and organ damages. This protein-mediated intervention provides the additional effect needed beyond lifestyle changes, enabling reversal of damages while maintaining glucose control

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent combines the effects of lifestyle modification with enolase 1 protein therapy to create a composite treatment approach. This combination achieves both glucose control and reversal of vascular and organ damages, overcoming the insufficiency of lifestyle changes alone

Inventive Principle:

Principle #40Composite materials

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

Eno1 treatment increases glucose uptake and insulin response, improving glucose tolerance and reducing HbA1c levels, effectively addressing impaired glucose metabolism and diabetes management.

Implementation Method 1

Enolase 1 (also known as Eno1, alpha-enolase, or non-neural enolase) is an enzyme that catalyzes the conversion of 2-phospho-D-glycerate to phosphoenolpyruvate in the glycolytic pathway

Methodology Applied

Scientific EffectEnzyme catalysis: Enzyme

Data Source

PatentUS11224641B2Enolase 1 (ENO1) compositions and uses thereof

Publication Date: 2022.01.18 BPGBIO INC

AI summary

The invention provides compositions comprising Eno1 for delivery to a muscle. Further, the invention provides a method for normalizing blood glucose in a subject with elevated blood glucose, comprising administering to the subject enolase 1 (Eno1), thereby normalizing blood glucose in the subject. The invention also provides methods of treating one or more conditions including impaired glucose tolerance, insulin resistance, pre-diabetes, and diabetes, especially type 2 diabetes in a subject, comprising administering to the subject enolase 1 (Eno1), thereby treating the condition in the subject. In certain methods of the invention, the Eno1 is delivered to muscle.