TRPM7 Channel Modulators for Ischemic Injury Treatment
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Solution Overview
Problem
Current therapies fail to effectively prevent neuronal death caused by TRPM7 channel activation during brain ischemia and ischemic injuries, as they do not adequately address the calcium overload and cell death triggered by extracellular divalent cation reductions.
Innovation Solution
Development of pharmaceutical compositions comprising specific compounds (e.g., M5, M6, M11, M14, M21) that inhibit TRPM7-mediated cell death by modulating the activity of the TRPM7 channel, thereby reducing ischemic damage and cell death in mammalian cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antiexcitotoxic therapies are used, then some neuronal protection may be achieved, but they fail to effectively prevent neuronal death caused by TRPM7 channel activation and calcium overload during brain ischemia
Solution Approach 1:
The patent extracts and targets the specific TRPM7 channel as the key mediator of ischemic injury, separating it from general excitotoxicity pathways. By focusing on TRPM7 channel activation and calcium overload specifically, the invention identifies a precise therapeutic target that current broad-spectrum antiexcitotoxic therapies miss, thereby resolving the contradiction between existing therapy effectiveness and the specific harmful mechanism of TRPM7-mediated cell death
Solution Approach 2:
The patent employs parameter changes by modulating TRPM7 channel activity through specific chemical compounds that alter channel gating, ion selectivity, or trafficking. These parameter changes in channel function directly address calcium overload and prevent the harmful effects of extracellular divalent cation reductions, improving neuronal survival without relying on non-specific excitotoxicity blockade
2Reliability
If TRPM7 channel activity is inhibited, then cell death and ischemic damage are reduced, but the mechanism of action and specific compound selection become more complex
Solution Approach 1:
The patent segments the TRPM7 channel into distinct functional domains (ion channel pore, kinase domain, regulatory sites) and identifies specific compounds that target different segments or aspects of channel function. This segmentation allows systematic exploration of inhibition mechanisms and facilitates rational drug design, reducing the complexity of compound selection while maintaining effective TRPM7 blockade
Solution Approach 2:
The patent introduces TRPM7 channel activity as an intermediary mechanism linking extracellular divalent cation reductions to neuronal death. By establishing this intermediary role, the invention simplifies the overall pathophysiology and enables targeted therapeutic intervention through compounds that specifically modulate TRPM7, thereby reducing the complexity of treating ischemic damage without requiring multiple simultaneous mechanisms
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 compounds significantly inhibit TRPM7-mediated cell death by at least 50% and are effective in treating or preventing ischemic damage, cancer, pain, and glaucoma by reducing cell death and proliferation, and inhibiting metastasis, demonstrating their potential in various therapeutic applications.
Implementation Method 1
TRPM7 channels are calcium-permeant ion channels that conduct calcium and other cations into cells through the membrane
Implementation Method 2
The compounds significantly inhibit TRPM7-mediated cell death by at least 50% and are effective in treating or preventing ischemic damage
Data Source
AI summary
This invention relates to methods of screening for modulators of mammalian cell injury cause by TRPM7 gene and protein activity, compounds that modulate TRPM7 gene and protein activity and methods of treatment of mammalian cell injury using modulators of TRPM7 gene and protein activity.