Neurotrophic Peptides Crossing Blood-Brain Barrier
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Solution Overview
Problem
Current treatments for neurodegenerative diseases face challenges due to the blood-brain barrier hindering the delivery of neurotrophic factors like CNTF, which also have short half-lives and require direct bolus injections, limiting their therapeutic effectiveness.
Innovation Solution
Development of neurotrophic and neurogenic peptides with specific amino acid sequences, such as VGDGGLFEKKL, EDQQVHFTPTEG, and IPENEADGMPATV, that can pass through the blood-brain barrier, offering comparable neurotrophic and neurogenic effects to wild-type CNTF and potentially being used in fusion or conjugation with other proteins to enhance delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If neurotrophic factors like CNTF are used to treat neurodegenerative diseases, then neurotrophic and neuroprotective effects are achieved, but the blood-brain barrier hinders their delivery to the brain
Solution Approach 1:
The patent segments the large CNTF protein into smaller peptide fragments (e.g., residues 1-11, 1-10, 2-11, etc.) that can penetrate the blood-brain barrier while retaining neurotrophic activity. This segmentation allows the therapeutic agent to overcome the barrier obstruction while maintaining its biological function.
Solution Approach 2:
The patent extracts specific active peptide sequences from the full-length CNTF protein that are responsible for neurotrophic effects. These extracted peptides (e.g., VGDGGLFEKKL, EDQQVHFTPTEG, IPENEADGMPATV) are small enough to cross the blood-brain barrier while preserving the essential therapeutic functionality.
2Reliability
If direct bolus injections of CNTF are administered, then neurotrophic effects are delivered, but the short half-life of CNTF limits therapeutic effectiveness
Solution Approach 1:
The patent uses small peptides with shorter half-lives that can be administered more frequently or at lower doses. These peptides, while having shorter duration of action individually, can achieve sustained therapeutic effects through repeated administration or combination therapy, overcoming the limitation of long half-life requirements.
Solution Approach 2:
The patent employs multiple different peptides (SEQ ID NO: 1, 2, 3 and their fragments) that can be used in combination or sequentially to maintain continuous neurotrophic support. This approach ensures sustained therapeutic action despite the short half-life of individual peptide administrations.
3Object-affected harmful factors
If small peptide fragments are used to cross the blood-brain barrier, then barrier penetration is improved, but the neurotrophic activity may be reduced compared to full-length CNTF
Solution Approach 1:
The patent identifies and utilizes specific local sequences within CNTF that possess neurotrophic activity. Different peptide fragments (e.g., VGDGGLFEKKL from residues 145-155, EDQQVHFTPTEG from residues 38-49, IPENEADGMPATV from residues 76-88) target specific receptors or pathways to achieve neuroprotection, allowing each fragment to function optimally in its specific context.
Solution Approach 2:
The patent combines multiple different peptide fragments in compositions that collectively provide neurotrophic effects comparable to full-length CNTF. The synergistic interaction of different peptides (SEQ ID NO: 1, 2, 3 and their fragments) compensates for the reduced activity of individual fragments, achieving both barrier penetration and therapeutic efficacy.
Data Source
AI summary
The present invention relates to a neurotrophic peptide having an amino acid sequence selected from the group consisting of VGDGGLFEKKL (SEQ ID NO: 1), EDQQVHFTPTEG (SEQ ID NO: 2) and IPENEADGMPATV (SEQ ID NO: 3).