mTORC1–MDK Combination Therapy for TSC-Associated AML and LAM

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Solution Overview

Problem

Current treatments for Tuberous Sclerosis Complex (TSC)-associated diseases such as angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM) are limited by therapeutic resistance and the inability to comprehensively address tumor cell heterogeneity and immune microenvironment interactions, leading to recurrent tumor growth and lung function decline.

Innovation Solution

Administering a combination of therapeutic agents targeting mTORC1 and MDK, optionally with checkpoint inhibitors, to enhance the efficacy of mTORC1 inhibition and overcome therapeutic resistance in TSC-associated diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If a single therapeutic agent targeting mTORC1 is used, then the treatment mechanism is simple, but therapeutic resistance develops and treatment efficacy is limited

Engineering Contradiction:

Improvetreatment efficacyVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent combines multiple therapeutic agents with different mechanisms of action (mTORC1 inhibitor, MDK inhibitor, and checkpoint inhibitor) into a composite treatment regimen. This merging of therapies addresses therapeutic resistance by targeting multiple pathways simultaneously, thereby improving treatment efficacy while managing the complexity through a structured combination approach

Inventive Principle:

Principle #5Merging (Combining)

2Adaptability or versatility

If conventional monotherapy is used, then the treatment approach is straightforward, but it cannot address tumor cell heterogeneity and immune microenvironment interactions

Engineering Contradiction:

Improveability to address tumor heterogeneityVSAvoidtreatment regimen complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The treatment regimen is segmented into distinct functional components: mTORC1 inhibition for direct tumor cell targeting, MDK inhibition for addressing tumor heterogeneity and stromal interactions, and checkpoint inhibition for modulating the immune microenvironment. This segmentation allows each agent to address specific aspects of tumor complexity while maintaining an organized treatment structure

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The combination therapy regimen is designed to perform multiple functions simultaneously: inhibiting tumor cell growth, addressing intra-tumoral heterogeneity, modulating the immune microenvironment, and overcoming therapeutic resistance. This multi-functionality enables a single treatment protocol to address various aspects of complex TSC-associated diseases

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentUS20250334588A1Treating tuberous sclerosis complex-associated diseases

Publication Date: 2025.10.30 THE BRIGHAM & WOMEN S HOSPITAL INC

AI summary

Provided herein are compositions and methods using a therapeutic agent targeting mTORCI and a therapeutic agent targeting MDK for treating a Tuberous Sclerosis Complex (TSC)-associated disease, e.g., Angiomyolipoma (AML) and lymphangioleiomyomatosis (LAM), or for treating sporadic LAM/AML. Also provided are methods of identifying subjects for treatment, e.g., with checkpoint inhibitors.