IL-18BP Isoforms Modulate Neuroinflammation
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Solution Overview
Problem
Current therapies for neurological and inflammatory diseases associated with neuro-inflammation, such as Alzheimer's, Parkinson's, and multiple sclerosis, are limited in effectively addressing the underlying inflammatory responses and promoting neurological recovery.
Innovation Solution
The use of IL-18BP isoforms, specifically IL-18BPb and IL-18BPd, which do not bind to IL-18, to reduce the secretion of pro-inflammatory cytokines like IL-6 and MCP-1, and induce STAT2 nuclear translocation, offering potential therapeutic benefits for these diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for neurological and inflammatory diseases, then treatment is provided, but they are limited in effectively addressing the underlying inflammatory responses and promoting neurological recovery
Solution Approach 1:
The patent uses IL-18BP isoforms (specifically IL-18BPb and IL-18BPd) as intermediary molecules that modulate the inflammatory response by binding to IL-18 and preventing it from activating its receptor. This intermediary approach allows the therapy to effectively address underlying inflammatory responses without directly targeting the root cause, thereby improving the reliability and adaptability of the treatment for neurological and inflammatory diseases.
2Reliability
If IL-18BP isoforms that do not bind to IL-18 are used, then anti-inflammatory effects are achieved by decreasing IL-6 and MCP-1 secretion, but this represents a novel approach rather than established therapy
Solution Approach 1:
The patent exploits parameter changes in the IL-18BP protein structure by using specific isoforms (IL-18BPb and IL-18BPd) that differ in their binding affinity to IL-18. These isoforms have modified parameters compared to the wild-type IL-18BP, allowing them to exert anti-inflammatory effects through alternative mechanisms (decreasing IL-6 and MCP-1 secretion) while maintaining therapeutic efficacy. This parameter-based approach enables the development of novel therapies with predictable and controllable anti-inflammatory effects.
Data Source
AI summary
The invention relates to the use of an IL18-BP isoform that does not bind to IL18, or of an agonist thereof, for treatment or prevention of a neurological and/or inflammatory disease. Preferred isoforms for use in the frame of the invention include IL-18BPb and IL-18BPd.