AMD3100 and Tacrolimus Combination for Allograft Tolerance

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current immunosuppressive regimens for organ transplantation are associated with significant side effects such as infections, diabetes, hypertension, and malignancy, and do not achieve long-term allograft acceptance without chronic immunosuppression.

Innovation Solution

Administering a stem cell mobilizer, such as AMD3100, in combination with a low dose of an immunosuppressive agent, like Tacrolimus, to promote allograft survival and induce long-term allograft acceptance by mobilizing CD34+ and/or CD133+ stem cells, which facilitates the repopulation of allografts with recipient-derived cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If standard immunosuppressive regimens are used to prevent graft rejection, then allograft survival is improved, but significant side effects occur including infections, diabetes, hypertension, and malignancy

Engineering Contradiction:

Improveallograft survivalVSAvoidside effects (infections, diabetes, hypertension, malignancy)

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the dosing parameters of immunosuppressive agents by administering lower doses in combination with stem cell mobilizers, thereby maintaining graft protection while reducing the intensity of immunosuppression to minimize side effects

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces stem cell mobilizers as intermediary agents that facilitate the recruitment and engraftment of recipient-derived stem cells in the allograft, creating a biological mechanism for tolerance that reduces dependence on high-dose immunosuppression

Inventive Principle:

Principle #24Intermediary (Mediator)

2Duration of action of stationary object

If chronic immunosuppression is maintained to ensure long-term allograft acceptance, then graft function is preserved, but quality of life and survival rates are reduced due to side effects

Engineering Contradiction:

Improvelong-term allograft acceptanceVSAvoidquality of life reduction and survival rate impact

Core Design Contradiction:

Duration of action of stationary objectVSObject-generated harmful factors

Solution Approach 1:

The patent enables the allograft to serve itself by recruiting recipient-derived stem cells that home to the graft and promote its survival and function, reducing the need for continuous external immunosuppressive intervention

Inventive Principle:

Principle #25Self-service

Solution Approach 2:

The patent administers stem cell mobilizers in the immediate post-transplantation period to facilitate early stem cell recruitment and engraftment, establishing a foundation for long-term graft acceptance before tapering immunosuppression

Inventive Principle:

Principle #10Preliminary action

3Reliability

If high doses of immunosuppressive agents are administered to prevent rejection, then allograft survival is improved, but the risk of infections and malignancy increases

Engineering Contradiction:

Improveallograft survivalVSAvoidrisk of infections and malignancy

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the dosage parameters from high-dose monotherapy to low-dose combination therapy with stem cell mobilizers, maintaining protective effect while reducing immunosuppressive intensity to lower infection and malignancy risk

Inventive Principle:

Principle #35Parameter changes

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

This approach enhances allograft survival, reduces the need for chronic immunosuppression, and minimizes side effects, allowing for improved survival and tolerance in organ transplant recipients, including those with ischemic injury and inflammatory bowel disease.

Implementation Method 1

administering a therapeutically effective amount of a stem cell mobilizer and an immunosuppressive agent... an agent that mobilizes CD34+ and/or CD133+ stem cells

Methodology Applied

Scientific EffectStem cell mobilization:

Implementation Method 2

administering a therapeutically effective amount of a stem cell mobilizer and an immunosuppressive agent... the immunosuppressive agent is Tacrolimus

Methodology Applied

Scientific EffectImmunosuppression:

Implementation Method 3

mobilizing CD34+ and/or CD133+ stem cells, which facilitates the repopulation of allografts with recipient-derived cells

Methodology Applied

Scientific EffectStem cell homing and engraftment:

Data Source

PatentUS20220184043A1Methods of treating inflammatory bowel disease with AMD3100 and tacrolimus

Publication Date: 2022.06.16 MEDREGEN LLC

AI summary

The present invention relates to the field of inflammatory bowel disease. In one aspect, the present invention provides methods for treating inflammatory bowel disease in a patient comprising administering to the patient a therapeutically effective amount of a stem cell mobilizer and an immunosuppressive agent. In particular embodiments, the present invention provides a method for treating inflammatory bowel disease in a patient comprising administering to the patient a therapeutically effective amount of an agent that mobilizes CD34+ and/or CD133+ stem cells and a low dose of an immunosuppressive agent.