Neublastin Polypeptide for Ischemic Tissue Vascularization
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Solution Overview
Problem
Current methods fail to effectively promote neovascularization and increase blood flow to ischemic tissues, which are crucial for treating conditions like ischemic heart disease, stroke, and diabetic ulcers, where impaired blood flow leads to tissue damage and complications.
Innovation Solution
Administration of a polypeptide with an amino acid sequence at least 80% identical to amino acids 15-113 of neublastin, which binds to a complex containing GFRalpha3 and RET, to enhance vascularization in tissues with impaired blood flow, either systemically or locally, including in extremities and transplanted organs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used to promote neovascularization, then treatment of ischemic conditions is attempted, but the methods fail to effectively increase blood flow and vascularization in ischemic tissues
Solution Approach 1:
The patent identifies and utilizes specific amino acid sequences (at least 80% identical to amino acids 15-113 of neublastin) that bind to the GFRalpha3-RET complex with high affinity. By changing the molecular parameters of the administered polypeptide to match this specific sequence identity threshold, the invention achieves reliable neovascularization promotion and significant blood flow increase in ischemic tissues, resolving the inadequacy of current methods.
2Productivity
If polypeptide administration is performed to increase vascularization, then blood flow to ischemic tissues is improved, but the polypeptide must maintain high sequence identity to neublastin to ensure effective binding to GFRalpha3-RET complex
Solution Approach 1:
The patent establishes a quantitative parameter threshold of at least 80% amino acid sequence identity to amino acids 15-113 of neublastin. This parameter definition balances manufacturing feasibility with biological effectiveness, allowing sufficient sequence variation while maintaining the critical binding affinity to the GFRalpha3-RET complex necessary for effective neovascularization promotion.
Solution Approach 2:
The invention focuses on a specific local region of the neublastin protein (amino acids 15-113) that contains the critical binding interface with the GFRalpha3-RET complex. By requiring high sequence identity in this specific local region rather than the entire protein sequence, the patent maintains binding effectiveness while allowing flexibility in other regions, thus resolving the contradiction between precision requirements and manufacturing ease.
3Adaptability or versatility
If systemic or local polypeptide administration is used, then vascularization is enhanced in various tissues including extremities and transplanted organs, but the treatment must be tailored to specific tissue types and delivery routes
Solution Approach 1:
The patent describes a universal polypeptide treatment approach where a single active ingredient (polypeptide with ≥80% identity to neublastin amino acids 15-113) can be administered via multiple routes (systemic or local) to treat various ischemic conditions including those in extremities and transplanted organs. This universal mechanism resolves the contradiction by providing adaptability across different tissues and delivery methods while maintaining a consistent core treatment strategy, thus avoiding excessive complexity.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The polypeptide significantly increases vascularization and blood flow to ischemic tissues, as demonstrated by increased capillary density and perfusion, thereby reducing tissue damage and improving outcomes in conditions characterized by impaired blood flow.
Implementation Method 1
the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET
Data Source
AI summary
Disclosed are methods of increasing vascularization in a tissue by administering a neublastin polypeptide to a mammal exhibiting impaired or inadequate blood flow in the tissue. The methods can be used to in the treatment or prevention of a disorder characterized by impaired or inadequate blood flow or to increase vascularization in an organ that has been transplanted into a subject.