Engineered Gut Bacteria for Oxalate Degradation in Hyperoxaluria
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for hyperoxaluria are limited, and patients struggle to effectively manage elevated oxalate levels, leading to conditions such as recurrent calcium oxalate kidney stones and kidney damage.
Innovation Solution
Modified bacteria with enhanced oxalate-degrading activity, engineered to express specific enzymes and pathways for oxalate metabolism, are administered to enhance oxalate breakdown in the body.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If a high-calcium, low-oxalate diet is prescribed, then oxalate absorption is reduced, but patient compliance is difficult to maintain and oxalate avoidance is insufficient
Solution Approach 1:
The engineered bacteria autonomously perform oxalate degradation within the patient's gut, eliminating the need for continuous patient compliance with dietary restrictions. The bacteria self-regulate oxalate breakdown through their metabolic pathways, providing a self-sustaining therapeutic effect that does not depend on patient behavior.
2Reliability
If pyridoxine is prescribed for primary hyperoxaluria, then some enzyme activity is salvaged, but treatment is only effective for specific genetic mutations
Solution Approach 1:
The engineered bacteria provide a universal oxalate degradation capability that addresses the underlying metabolic defect across all forms of hyperoxaluria, regardless of the specific genetic mutation. By introducing exogenous oxalate-metabolizing pathways into the gut microbiome, the treatment becomes applicable to primary hyperoxaluria types I, II, and III, as well as secondary forms, making it a versatile therapy that transcends genetic specificity.
3Reliability
If liver transplant is performed, then missing liver enzymes are replaced, but treatment is invasive and not suitable for all patients
Solution Approach 1:
Instead of directly replacing liver enzymes through invasive transplantation, the patent uses engineered gut bacteria as intermediary organisms that perform oxalate degradation in the gastrointestinal tract. These bacteria act as a mediator between the patient's metabolic needs and the oxalate load, providing enzyme functionality without requiring liver transplantation or direct intervention in liver physiology.
4Quantity of substance
If oxalate is eliminated through urine, then oxalate disposal occurs, but hyperoxaluria develops when excessive oxalate is excreted
Solution Approach 1:
The patent converts the harmful excess oxalate into beneficial metabolic products by introducing bacteria that degrade oxalate into less harmful substances. The oxalate degradation pathway transforms oxalate into intermediates like glyoxylate and formate, which can then be further metabolized or excreted in safer forms, effectively converting the toxic substance into beneficial or harmless end products.
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 bacteria effectively reduce oxalate levels, providing a powerful and stable treatment option for hyperoxaluria, potentially reducing the risk of kidney stones and renal damage.
Implementation Method 1
engineered to express specific enzymes and pathways for oxalate metabolism
Implementation Method 2
enhanced oxalate degrading activity relative to a similar or otherwise identical bacterium that has not been modified
Data Source
AI summary
The disclosure relates generally to bacteria that have been modified to have increased oxalate degrading activity, pharmaceutical compositions including the bacteria, and methods of treating disorders associated with an elevated amount of oxalate, e.g., hyperoxaluria.