Cyclized IGFBP Peptide Fragments for CNS Disease Modification
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Solution Overview
Problem
Current treatments for neurodevelopmental disorders such as Phelan-McDermid Syndrome and other central nervous system disorders like autism spectrum disorders and depression are limited, with no disease-modifying therapies available, and existing interventions are costly and have varying degrees of effectiveness due to the disorder's immense etiological heterogeneity.
Innovation Solution
Development of isolated insulin-like growth factor binding protein (IGFBP) peptide fragments, specifically peptides with sequences such as KHGLYNLKQCKMSLNGQ and PKKLRP, which are cyclized and modified with N-terminal carboxylation and C-terminal amidation, for administration to treat these disorders, offering therapeutic benefits.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for neurodevelopmental disorders, then current management can be provided, but no disease-modifying therapy is available and treatments are costly
Solution Approach 1:
The patent segments the full-length IGFBP proteins into specific peptide fragments (e.g., residues 1-20, 21-40, or 41-60) that retain biological activity. This segmentation allows for smaller, potentially less costly molecules that can achieve disease modification without requiring the full protein structure, thus addressing both the need for disease-modifying therapy and reducing treatment cost.
Solution Approach 2:
The patent extracts specific functional domains from the IGFBP proteins, isolating peptide fragments that contain the essential bioactive sequences. By taking out only the necessary portions rather than using the complete protein, the invention reduces molecular complexity and potential treatment cost while maintaining the ability to provide disease-modifying therapy.
2Adaptability or versatility
If existing interventions are used, then treatment can be provided, but effectiveness varies due to etiological heterogeneity
Solution Approach 1:
The patent develops IGFBP peptide fragments that can potentially treat multiple neurodevelopmental disorders (Phelan-McDermid Syndrome, autism spectrum disorders, depression) with a single therapeutic agent. This multi-functionality addresses the etiological heterogeneity by finding a common therapeutic target across different disorders, thereby improving adaptability while enhancing reliability through a unified treatment approach.
3Reliability
If full-length IGFBP proteins are used, then therapeutic effect can be achieved, but molecular complexity and potential side effects increase
Solution Approach 1:
The patent divides the full-length IGFBP protein into smaller peptide fragments that maintain therapeutic activity. This segmentation reduces molecular complexity, making the molecules easier to synthesize and administer, while the retained bioactive sequences ensure therapeutic effect is maintained.
Solution Approach 2:
The patent extracts and utilizes only the essential functional sequences from the full-length proteins, removing unnecessary regions that would increase molecular complexity. This extraction approach maintains the core therapeutic effect while significantly reducing the size and complexity of the molecules.
Data Source
AI summary
Described herein are isolated peptides, compositions comprising the same, and methods of using such peptides or compositions in the treatment of depression, central nervous system disorders, and neurodevelopmental disorders.