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, and existing methods for overcoming this barrier are not optimal.
Innovation Solution
Development of neurotrophic and neurogenic peptides with specific amino acid sequences, such as VGDGGLFEKKL, EDQQVHFTPTEG, or IPENEADGMPATV, that can pass through the blood-brain barrier and exhibit comparable or enhanced neurotrophic effects to wild-type CNTF, allowing for direct action on neural tissues.
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 neural tissues
Solution Approach 1:
The patent segments the large CNTF protein into smaller peptide fragments (e.g., residues 145-155: VGDGGLFEKKL) that can penetrate the blood-brain barrier while retaining neurotrophic activity. This segmentation allows the active moiety to reach the brain without the size and complexity constraints of the full-length protein.
Solution Approach 2:
The patent extracts the essential neurotrophic moiety from the complete CNTF protein structure. By identifying and isolating the critical amino acid sequence (residues 145-155) responsible for neurotrophic activity, the invention creates a minimal effective fragment that can cross the blood-brain barrier and exert therapeutic effects without requiring the full protein structure.
2Ease of operation
If existing methods are used to overcome the blood-brain barrier, then delivery to neural tissues is achieved, but the methods are not optimal and may be invasive
Solution Approach 1:
The patent changes the physical parameter of the therapeutic agent from a large protein (CNTF, 200 amino acids) to a small peptide fragment (11 amino acids: VGDGGLFEKKL). This parameter change in molecular size and structure enables passive diffusion across the blood-brain barrier without requiring invasive delivery devices or complex administration procedures.
3Reliability
If full-length CNTF is used, then strong neurotrophic effects are achieved, but the molecule is too large to cross the blood-brain barrier effectively
Solution Approach 1:
The patent creates a simplified copy or representation of the essential neurotrophic function using only the critical 11 amino acid sequence (VGDGGLFEKKL) from residues 145-155 of CNTF. This copied sequence replicates the neurotrophic activity necessary for therapeutic effect while being small enough to cross the blood-brain barrier, eliminating the need for the full-length protein.
Data Source
AI summary
The present invention relates to a neurotrophic peptide having an amino acid sequence of VGDGGLFEKKL (SEQ ID NO: 1) and alternatively comprising an adamantyl group at the C-and/or N-terminal end. The neurotrophic peptide can rescue cognition, correct impairments in neural cell proliferation and synaptic plasticity, and thus address the cognitive defects associated with Alzheimer's disease.