Queuine-Insertase Substrates Modulate Th Cell Differentiation
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Solution Overview
Problem
Current treatments for multiple sclerosis are inadequate in effectively managing the disease, with existing medications having adverse effects and limited ability to alter the disease's progression, and there is a need for more tolerable and effective therapies.
Innovation Solution
Development of molecules that act as substrates for the queuine-insertase enzyme complex, specifically targeting the imbalance of Th cell function and differentiation to regulate autoimmune responses, thereby reducing inflammation and autoimmune disease activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current medications are used to treat multiple sclerosis, then disease progression is partially managed, but adverse effects occur and tolerance is poor
Solution Approach 1:
The patent changes the molecular target parameter from conventional immune modulators to queuine-insertase enzyme substrates, which specifically modulate Th cell differentiation. This parameter change results in molecules that reduce interferon gamma production and shift the balance toward regulatory T cells, achieving disease management with fewer adverse effects and better patient tolerance.
Solution Approach 2:
The patent introduces queuine-insertase enzyme substrates as intermediary molecules that mediate immune response modulation. These substrates act through the queuine-insertase enzyme complex to regulate Th cell differentiation, serving as a novel intermediary mechanism between the administered drug and the immune system, thereby achieving effective disease management with improved safety profile.
2Reliability
If conventional treatments are used, then relapse rate is reduced to some extent, but ability to alter disease progression is limited
Solution Approach 1:
The patent employs preliminary action by using queuine-insertase substrates that proactively modulate Th cell differentiation before disease progression occurs. These molecules prevent the formation of pathogenic Th1 and Th17 cells and promote regulatory T cell development, thereby altering disease progression trajectory rather than merely responding to relapses after they occur.
Solution Approach 2:
The patent changes the therapeutic parameter from passive relapse reduction to active disease progression modulation by targeting Th cell differentiation. This parameter change enables the treatment to alter the fundamental course of the disease by shifting immune response parameters, thereby improving both relapse rate reduction and disease progression alteration capability.
3Reliability
If existing therapies are administered, then immune response is modulated, but interferon gamma production remains elevated
Solution Approach 1:
The patent uses queuine-insertase substrates as intermediary molecules that specifically target interferon gamma production. These substrates act through the queuine-insertase enzyme complex to modulate Th cell differentiation, thereby reducing interferon gamma secretion while maintaining effective immune response modulation. This intermediary mechanism enables selective reduction of pathogenic cytokines without compromising overall immune function.
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 molecules effectively lower interferon gamma production and modulate immune responses, potentially offering a more effective and tolerable treatment option for multiple sclerosis by suppressing effector T cells and enhancing regulatory T cells, thereby halting and reversing disease progression.
Implementation Method 1
Molecules which can exploit an enzyme complex made of two proteins, tRNA guanine transglycosylase (TGT) also known as queuine tRNA-ribosyltransferase 1, and queuine tRNA-ribosyltransferase domain containing 1 (QTRTD1), subsequently referred to as the queuine-insertase enzyme complex
Data Source
AI summary
The invention provides a novel approach to the treatment of autoimmune diseases, particularly multiple sclerosis, using a molecule capable of acting as substrate for the queuine-insertase enzyme complex.