Modified GDF15 Peptides for Metabolic Disorder Treatment
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Solution Overview
Problem
Current pharmacological treatments for obesity and diabetes, such as appetite suppressors and nutrient-absorption inhibitors, are ineffective and often cause severe adverse effects, and there is a need for alternative modalities that can modulate appetite, glucose, and insulin levels to effectively treat metabolic disorders.
Innovation Solution
The use of modified human Growth Differentiation Factor 15 (GDF15) molecules, including muteins and variants, which can bind to GDF15 receptors to initiate signal transduction pathways, reducing body weight and improving glucose metabolism, is contemplated, along with nucleic acid molecules encoding these peptides and their formulations for therapeutic use.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current pharmacological treatments (appetite suppressors, nutrient-absorption inhibitors) are used, then obesity treatment is attempted, but severe adverse effects occur and effectiveness is insufficient
Solution Approach 1:
The patent modifies the GDF15 protein sequence through specific amino acid substitutions (e.g., at positions 62, 69, 91, 107) and glycosylation modifications to alter its biological properties. These parameter changes in the protein structure enable enhanced binding affinity to GDF15 receptors and improved pharmacokinetic characteristics, resulting in effective weight loss without severe adverse effects while maintaining safety profile
Solution Approach 2:
The modified GDF15 molecule acts as an intermediary substance that mediates between the administration system and the target biological pathways. The protein serves as a carrier that delivers specific biological activities through receptor binding, enabling controlled modulation of appetite and metabolism without direct toxic effects on the patient
2Weight of moving object
If modified GDF15 molecules are administered, then body weight reduction is achieved, but plasma glucose levels may be affected
Solution Approach 1:
The patent introduces local quality modifications through site-specific glycosylation at particular positions in the GDF15 sequence. These localized glycosylation modifications enhance the protein's binding specificity to certain receptor subtypes while maintaining overall metabolic regulation, enabling weight loss with preserved glucose homeostasis through differentiated receptor engagement
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 modified GDF15 molecules demonstrate therapeutic effectiveness in reducing body weight, lowering plasma glucose, and improving glucose tolerance, offering a potential alternative to existing treatments for obesity and diabetes by effectively modulating metabolic pathways.
Implementation Method 1
which can bind to GDF15 receptors to initiate signal transduction pathways
Data Source
AI summary
Methods of treating individuals with a glucose metabolism disorder and/or a body weight disorder, and compositions associated therewith, are provided.