TOMM6-Interacting Compounds for Mitochondrial Dysfunction and Protein Aggregation

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Solution Overview

Problem

Current treatments for nervous system diseases, atherosclerosis, Hepatitis B infection, and HPV infection are inadequate, with existing therapies offering limited efficacy and significant side effects, and there is a need for disease-modifying approaches that target mitochondrial dysfunction and protein aggregation.

Innovation Solution

Development of TOMM6-interacting compounds that bind, induce, or stabilize the Translocase of Outer Membrane 6kDa subunit homologue (TOMM6) to prevent mitochondrial dysfunction, toxic protein aggregation, and inhibit amyloidogenic protein assembly, thereby treating or preventing the mentioned conditions.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for nervous system diseases are used, then disease symptoms can be managed, but they cannot modify disease progression and have major side effects

Engineering Contradiction:
Improvedisease modification capabilityVSAvoidside effects
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses TOMM6 as an intermediary target - a mitochondrial outer membrane protein involved in protein import - to mediate the therapeutic effect. By developing compounds that specifically interact with TOMM6, the invention creates a new pathway for disease modification that avoids the side effects of conventional treatments. The TOMM6-interacting compounds act as intermediaries between the administered drug and the pathological processes, enabling selective modulation of mitochondrial function and protein aggregation without affecting other systems.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the therapeutic parameter from symptomatic management to disease modification by targeting mitochondrial protein import machinery. The TOMM6-interacting compounds alter the fundamental parameter of mitochondrial function and protein aggregation dynamics, representing a paradigm shift from managing symptoms to modifying the underlying disease progression mechanism.

Inventive Principle:
Principle #35Parameter changes

2Quantity of substance

If approaches that only interfere with Abeta plaque formation are used, then plaque accumulation may be reduced, but they do not demonstrate efficacy in retarding AD progression and show major side effects

Engineering Contradiction:
ImproveAbeta plaque formationVSAvoiddisease progression retardation
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent extracts the therapeutic focus from merely reducing Abeta plaque quantity to addressing the underlying mitochondrial dysfunction and protein aggregation mechanisms. By taking out the TOMM6 target from the conventional amyloid-centric approach and developing specific TOMM6-interacting compounds, the invention creates a more comprehensive treatment that addresses multiple pathological features simultaneously, including protein aggregation, mitochondrial dysfunction, and neuroprotection.

Inventive Principle:
Principle #2Taking out (Extraction)

3Reliability

If TOMM6-interacting compounds are developed, then mitochondrial dysfunction and protein aggregation can be targeted, but new therapeutic agents with unknown safety profiles are introduced

Engineering Contradiction:
Improvemitochondrial function stabilizationVSAvoidunknown safety profile
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The TOMM6-interacting compounds enable the cell's own mitochondrial import machinery to function properly by stabilizing TOMM6 protein levels and activity. Rather than introducing foreign molecules that disrupt cellular processes, the compounds facilitate the cell's natural protein import functions, allowing mitochondria to self-regulate their protein composition and maintain proper function. This self-service approach reduces the risk of adverse effects.

Inventive Principle:
Principle #25Self-service

Data Source

PatentEP3801507B1TOMM6-interacting extracts and compounds for use in the treatment and prophylaxis of nervous system diseases, atherosclerosis, hepatitis b infection and human papilloma virus (HPV) infection
Publication Date: 2025.01.01 ETH ZURICH
  • EP3801507B1 patent drawingFigure 1A~1C
  • EP3801507B1 patent drawingFigure 2A~2B
  • EP3801507B1 patent drawingFigure 3A~3B

AI summary

The present invention is directed to a TOMM6 (Translocase of Outer Membrane 6kDa subunit homologue; Mitochondrial import receptor subunit TOM6 homolog)-interacting plant or fungal extract comprising an anthraquinone or anthraquinone derivative, a TOMM6-interacting anthraquinone or anthraquinone derivative, and TOMM6-interacting compounds for use in the treatment or prophylaxis of a nervous system disease, atherosclerosis, Hepatitis B infection and/or human papilloma virus (HPV) infection. Furthermore, the present invention relates to a corresponding method of therapeutic or prophylactic treatment of a nervous system disease or disorder, atherosclerosis, Hepatitis B infection and/or human papilloma virus (HPV) infection, as well as to a method for the identification of a TOMM6-interacting compound or composition. Also, the present invention provides a non-human transgenic animal expressing a transgenic, preferably human TOMM6 or a TOMM6 homolog.