FGF2/FGF1 Chimeric Proteins for Metabolic Disease Treatment

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current insulin sensitizers for type 2 diabetes, such as thiazolidinediones, have significant side effects including weight gain, liver toxicity, and other adverse reactions, necessitating the development of new treatments that effectively reduce blood glucose levels without these complications.

Innovation Solution

Development of FGF2/FGF1 chimeric proteins, which combine an N-terminal portion of fibroblast growth factor 2 (FGF2) with a C-terminal portion of FGF1, achieving at least 95% sequence identity to specific sequences, to administer therapeutically effective amounts that reduce blood glucose levels and treat metabolic diseases like type 2 diabetes.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If thiazolidinedione (TZD) class insulin sensitizers are used to treat type 2 diabetes, then blood glucose levels are reduced, but significant side effects occur including weight gain, liver toxicity, and other adverse reactions

Engineering Contradiction:
Improveblood glucose reduction efficacyVSAvoidside effects including weight gain, liver toxicity, and adverse reactions
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the molecular structure of FGF2 by fusing it with the C-terminal portion of FGF1, creating chimeric proteins with altered properties. This structural parameter change results in a new therapeutic agent that maintains glucose-lowering efficacy while reducing adverse effects associated with conventional TZD drugs

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The invention creates composite proteins by combining functional domains from two different FGF molecules (FGF2 and FGF1). The chimeric structure integrates the N-terminal portion of FGF2 with the C-terminal portion of FGF1, producing a hybrid molecule with improved therapeutic profile compared to single-source proteins

Inventive Principle:
Principle #40Composite materials

2Object-affected harmful factors

If new insulin sensitizers are developed to replace TZDs, then side effects are reduced, but the challenge remains to maintain effective blood glucose reduction

Engineering Contradiction:
Improveside effects reductionVSAvoidblood glucose reduction efficacy
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The chimeric FGF2/FGF1 proteins exhibit multiple therapeutic functions: they improve insulin sensitivity, reduce blood glucose levels, and decrease systemic inflammation. This multi-functionality allows the single agent to address multiple aspects of metabolic syndrome while maintaining efficacy comparable to or exceeding conventional treatments

Inventive Principle:
Principle #6Universality (Multi-functionality)

Data Source

PatentUS9925243B2Chimeric fibroblast growth factor (FGF) 2/FGF1 peptides and methods of use
Publication Date: 2018.03.27 SALK INST FOR BIOLOGICAL STUDIES
  • US9925243B2 patent drawing

AI summary

The present disclosure provides chimeric proteins having an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor (FGF) 2 and the C-terminus comprises a portion of an FGF1 protein, wherein the chimeric protein comprises at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12 or 13. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.