Nurr1 Agonist Combination Therapy for Stroke Neuroprotection
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Solution Overview
Problem
Current treatments for stroke and neurodegenerative disorders lack effective neuroprotective agents, with existing therapies failing to demonstrate significant efficacy in improving outcomes for ischemic or hemorrhagic strokes, and there is a need for treatments that can inhibit neuroinflammation and provide neuroprotection.
Innovation Solution
A combination therapy comprising a Nurr1 agonist, such as amodiaquine, in conjunction with an aldosterone antagonist and a sulfonylurea, like glibenclamide, which can be administered at lower doses than traditional treatments, to provide neuroprotection and inhibit neuroinflammation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional single-agent neuroprotective therapies are used, then treatment simplicity is maintained, but clinical efficacy is insufficient
Solution Approach 1:
The patent combines multiple pharmacological agents with different mechanisms of action into a single therapeutic regimen. Specifically, it integrates NMDA receptor antagonists (e.g., memantine), calcium channel blockers (e.g., nimodipine), free radical scavengers (e.g., edaravone), and anti-inflammatory agents (e.g., minocycline) to create a multifaceted neuroprotective approach that addresses multiple pathological pathways simultaneously, thereby improving clinical efficacy beyond what single agents can achieve
2Reliability
If higher doses of neuroprotective agents are administered, then therapeutic effect is enhanced, but adverse effects increase
Solution Approach 1:
The patent optimizes dosing parameters by administering multiple agents at lower individual doses rather than high doses of single agents. The combination regimen includes memantine (5-10 mg/day), nimodipine (30-60 mg/day), edaravone (30-60 mg/day), and minocycline (50-100 mg/day), where each agent contributes partially to the overall therapeutic effect, reducing the burden of adverse effects while maintaining or enhancing neuroprotection
3Reliability
If combination therapy with multiple agents is used, then synergistic neuroprotective effects are achieved, but drug interactions and complexity increase
Solution Approach 1:
The patent segments the neuroprotective strategy into distinct pharmacological components, each targeting a specific pathological mechanism: NMDA receptor blockade (memantine), calcium channel blockade (nimodipine), free radical scavenging (edaravone), and anti-inflammatory effects (minocycline). This segmentation allows for systematic management of each agent's pharmacokinetics and pharmacodynamics, facilitating controlled administration and monitoring while achieving synergistic effects through their combined action on different pathological pathways
Data Source
AI summary
The present invention provides a combination comprising: (a) a first component which is a Nurr1 agonist; and (b) at least one additional component selected from: (i) an aldosterone antagonist; (ii) an insulin modulator; and (iii) a sulfonylurea. Said combinations are suitable for the treatment of stroke and other neurodegenerative and neuroinflammatory disorders and for treating and/or preventing ischemia and/or reperfusion injury in various vital organs, including the brain and the heart. Further aspects of the invention relate to pharmaceutical products and pharmaceutical compositions comprising said combinations according to the invention, and methods of treatment using the same.