TML and TMAO Biomarker Detection for CKD Risk-Guided Treatment
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Solution Overview
Problem
Current treatments for chronic kidney disease (CKD) and related conditions such as heart failure are inadequate, as they do not emulate continuous kidney function, leading to fluid accumulation and increased mortality, and existing methods like dialysis are inconvenient, costly, and risky.
Innovation Solution
Identifying and treating subjects with elevated levels of N6-trimethyl-lysine (TML) or TML combined with trimethylamine-n-oxide (TMAO) using therapeutic agents that inhibit the TMA/FMO3/TMAO pathway, antibiotics, or dietary modifications to manage these conditions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If dialysis is used to treat CKD, then waste components and excess fluid are removed from blood, but treatment is intermittent and does not emulate continuous kidney function
Solution Approach 1:
The patent uses small molecules that can be administered orally or via other convenient routes to inhibit the TMA/FMO3/TMAO pathway, allowing the body's own metabolic processes to continuously manage fluid and waste without requiring external mechanical intervention like dialysis machines
Solution Approach 2:
The patent replaces the mechanical dialysis system with a biochemical approach using small molecule inhibitors that target the TMA/FMO3/TMAO pathway, substituting a complex mechanical extracorporeal system with a simple pharmacological intervention that works continuously within the body
2Reliability
If frequency and duration of dialysis sessions are increased, then survivability of dialysis patients is improved, but discomfort, inconvenience and costs associated with treatment increase
Solution Approach 1:
The patent achieves continuous therapeutic action through oral administration of small molecule inhibitors that maintain constant inhibition of the TMA/FMO3/TMAO pathway, eliminating the need for repeated intermittent dialysis sessions and providing uninterrupted physiological support
Solution Approach 2:
The body's metabolic systems continue to function naturally with the aid of small molecule inhibitors, allowing continuous self-regulation of fluid and waste management without requiring repeated external mechanical interventions
3Reliability
If extracorporeal processing of body fluids is performed, then waste components are removed from blood, but additional risk of infection is introduced
Solution Approach 1:
The patent enables the body to perform waste removal internally through inhibition of the TMA/FMO3/TMAO pathway, eliminating the need to extract blood and process it externally, thereby avoiding infection risks associated with vascular access and extracorporeal circuits
Solution Approach 2:
The patent replaces the extracorporeal mechanical processing system with an in vivo biochemical intervention, substituting a system that requires blood extraction and external processing with one that works entirely within the body's natural physiological environment
Data Source
AI summary
The present invention relates to systems, kits, and methods for identifying subjects with increased levels of N6-trimethyl-lysine (TML) or the combination of TML and trimethylamine-n-oxide (TMAO), as well as methods of determining risk of disease (e.g., kidney disease or heart failure) based on such levels. In certain embodiments, subjects with elevated TML, or TML and TMAO are treated with a therapeutic (e.g., one that inhibits the TMA/FMO3/TMAO pathway).