Engineered GFRAL Peptides for Weight and Nausea Modulation
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Solution Overview
Problem
There is a need for effective therapeutic treatments to manage chronic diseases such as cachexia, nausea, and emesis, as well as regulate weight and sexual dysfunction, as existing treatments are inadequate and can limit drug efficacy due to patient intolerance.
Innovation Solution
Development of engineered peptides that act as agonists or antagonists of the GDNF family receptor alpha-like (GFRAL) receptor, which can be administered to modulate anorectic/nausea/emesis responses and influence energy balance regulation, weight management, and sexual behaviors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments are used for cachexia, nausea, and emesis, then some therapeutic effect is achieved, but patient intolerance limits drug efficacy and tolerable dosage
Solution Approach 1:
The invention changes the chemical structure parameters by designing engineered peptides with modified amino acid sequences that maintain or enhance therapeutic efficacy while reducing immunogenicity and patient intolerance. The peptides are engineered with specific sequence variations from natural GDF15 to optimize binding affinity and reduce adverse immune responses.
Solution Approach 2:
The invention creates composite therapeutic molecules by fusing GDF15 peptide sequences with other functional domains or modifying residues to combine multiple properties: high receptor affinity, reduced immunogenicity, and improved pharmacokinetic characteristics, resulting in peptides that overcome the limitations of existing single-function treatments.
2Reliability
If GDF15 peptide is administered to activate GFRAL receptor, then anorectic and anti-emetic effects are achieved, but the peptide may have limited stability and half-life
Solution Approach 1:
The invention modifies physical-chemical parameters of the GDF15 peptide including amino acid composition, charge distribution, and structural conformation to enhance stability against proteolytic degradation and extend circulation half-life while maintaining biological activity at the GFRAL receptor.
Solution Approach 2:
The invention designs multiple variants of GDF15 peptides with different stability characteristics, allowing selection of the most appropriate peptide for specific therapeutic applications, and enables repeated dosing strategies with optimized pharmacokinetic profiles.
3Reliability
If engineered peptides are designed to target GFRAL receptor, then specific therapeutic effects are achieved, but the complexity of peptide design and manufacturing increases
Solution Approach 1:
The invention segments the GDF15 peptide into modular domains with specific functions (receptor binding domain, stability domain, etc.), allowing independent optimization of each domain and simplified manufacturing through modular assembly of standardized peptide building blocks.
Solution Approach 2:
The invention optimizes manufacturing parameters by designing peptides with amino acid compositions that favor simplified synthesis routes, reduced purification complexity, and enhanced stability during storage and processing, balancing therapeutic specificity with manufacturing feasibility.
Data Source
AI summary
The present invention relates to engineered peptides and to methods of making engineered peptides. The present invention also relates to methods of treatment comprising administration of the engineered peptides to a subject in need thereof.