Peptide Agents for Endogenous Testosterone Production

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Solution Overview

Problem

Current treatments for hypogonadism, such as testosterone replacement therapy, come with side effects like increased prostate cancer risk, cardiovascular events, and fluctuations in testosterone levels, and do not address the underlying mechanisms of testosterone production in testicular Leydig cells.

Innovation Solution

Development of peptide agents, specifically peptides comprising the 14-3-3ε binding motif, like RVTQSNF, that limit the interaction between 14-3-3ε and VDAC1 proteins to promote endogenous testosterone production without altering luteinizing hormone levels, along with screening assays to identify similar therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If testosterone replacement therapy is used to treat hypogonadism, then testosterone levels are restored, but the risk of prostate cancer, cardiovascular events, and other side effects increases

Engineering Contradiction:

Improvetestosterone levelsVSAvoidprostate cancer risk, cardiovascular events

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and targets the specific molecular mechanism (STAR-14-3-3ε complex) that controls testosterone production, separating the treatment from general testosterone replacement and focusing on restoring natural production through precise molecular intervention

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses small molecules that bind to 14-3-3ε as intermediaries to disrupt the STAR-14-3-3ε complex, thereby indirectly stimulating testosterone production without directly administering testosterone, thus avoiding the harmful effects of exogenous testosterone

Inventive Principle:

Principle #24Intermediary (Mediator)

2Ease of operation

If testosterone replacement therapy is administered, then symptoms of low testosterone are treated, but luteinizing hormone production is suppressed

Engineering Contradiction:

Improvesymptom treatmentVSAvoidluteinizing hormone production

Core Design Contradiction:

Ease of operationVSQuantity of substance

Solution Approach 1:

The patent enables the body's own testicular Leydig cells to resume testosterone production by blocking the inhibitory 14-3-3ε interaction, allowing the natural feedback loop to restore both testosterone and luteinizing hormone production without external intervention

Inventive Principle:

Principle #25Self-service

3Stability of the object's composition

If traditional testosterone replacement therapy is used, then testosterone levels are maintained, but fluctuations and skin irritation occur

Engineering Contradiction:

Improvetestosterone levelsVSAvoidfluctuations, skin irritation

Core Design Contradiction:

Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent replaces the mechanical delivery system (topical applications, injections) with a molecular mechanism-based approach that activates endogenous production, eliminating skin contact and the associated irritation and fluctuation problems

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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

These peptide agents effectively increase testosterone production in a manner independent of luteinizing hormone, reducing the risk of side effects associated with traditional therapies and providing a more stable and natural approach to addressing hypogonadism symptoms.

Implementation Method 1

The peptide-based agents comprise 14-3-3ε binding motifs and are shown to limit or impede the association between the 14-3-3ε protein and the VDAC1 protein

Methodology Applied

Scientific EffectProtein-protein interaction:

Implementation Method 2

Cholesterol import from cytosolic sources into mitochondria is a hormone-sensitive and rate-limiting step of steroidogenesis

Methodology Applied

Scientific EffectCholesterol transport:

Implementation Method 3

Cholesterol import into mitochondria is mediated by a hormone-induced multiprotein complex called the transduceosome, which is composed of cytosolic and outer mitochondrial membrane (OMM) proteins

Methodology Applied

Scientific EffectHormone-induced protein complex formation:

Implementation Method 4

the OMM high-affinity cholesterol-binding protein translocator protein (TSPO), which contains a cytosolic cholesterol recognition/interaction domain (CRAC)

Methodology Applied

Scientific EffectCholesterol recognition and binding:

Implementation Method 5

Cholesterol is cleaved into pregnenolone by CYP11A1 in mitochondria, and steroidogenesis begins

Methodology Applied

Scientific EffectEnzymatic cleavage: Enzyme

Data Source

PatentUS10301357B2Therapeutics for the induction of endogenous steroidogenesis and methods associated with their identification

Publication Date: 2019.05.28 ACESIS BIOMED US INC

AI summary

The present disclosure provides agents capable of promoting endogenous steroid production (such as endogenous testosterone production) without altering the endogenous luteinizing hormone. The present disclosure also provides associated therapeutic methods as well as screening assays for identifying further therapeutic agents for the prevention, treatment and/or alleviations of symptoms associated with hypogonadism.