BOS Risk Biomarker Detection After Hematopoietic Cell Transplant
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Solution Overview
Problem
Current diagnostic modalities for bronchiolitis obliterans syndrome (BOS) in hematopoietic stem cell transplant (HSCT) recipients, particularly children, are inadequate, leading to delayed identification and irreversible lung injury due to nonspecific symptoms and the inability to predict which patients will develop BOS, necessitating novel biomarkers and treatments.
Innovation Solution
Detection and quantification of biomarkers such as integrin-linked protein kinase (ILK), Kelch-like protein 5 (KLHL5), kinesin-like protein 22 (KID), SAC3 domain-containing protein 1 (SAC3D1), RRP12-like protein (PRP12), manganese transporting protein ATPase13A1 (ATP13A1), sorting nexin 8 (SNX8), caspase 8 associated protein 2 (CASP8AP2), and complement pathway components, followed by comparison to control values, to identify individuals at risk for BOS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If spirometry is used for diagnosing BOS in children after HSCT, then pulmonary function can be assessed, but reliable results are rarely obtained due to inconsistent effort and coordination in performing forced expiratory maneuvers
Solution Approach 1:
The patent replaces the mechanical spirometry system with a biomarker-based diagnostic approach. Instead of relying on mechanical lung function measurements that require patient coordination, the invention uses detection of specific biomarkers (such as ILK, KLHL5, KID, SAC3D1, PRP12, ATP13A1, SNX8, CASP8AP2, and complement pathway components) in blood or other biological samples to diagnose BOS, eliminating the need for forced expiratory maneuvers.
Solution Approach 2:
The patent introduces biomarkers as intermediary substances that mediate the diagnosis between the underlying BOS condition and the diagnostic test. These biomarkers serve as measurable indicators that reflect BOS pathophysiology without requiring direct measurement of lung mechanics, thereby solving the coordination problem in pediatric patients.
2Loss of time
If spirometry is used to detect BOS, then pulmonary complications can be identified, but diagnosis is delayed until irreversible lung injury occurs due to inability to perform reliable testing in most children
Solution Approach 1:
The patent enables preliminary detection of BOS through biomarker identification before irreversible lung injury occurs. By detecting biomarkers such as integrin-linked protein kinase (ILK), Kelch-like protein 5 (KLHL5), kinesin-like protein 22 (KID), SAC3 domain-containing protein 1 (SAC3D1), RRP12-like protein (PRP12), manganese transporting protein ATPase13A1 (ATP13A1), sorting nexin 8 (SNX8), caspase 8 associated protein 2 (CASP8AP2), and complement pathway components in blood or other biological samples, the system can identify BOS at an early stage when intervention is still effective.
Solution Approach 2:
The patent establishes a feedback mechanism where biomarker levels provide continuous information about BOS risk and progression. This allows for early detection and monitoring, enabling timely intervention to prevent irreversible lung injury before the disease progresses to a point where spirometry would be reliable but damage has already occurred.
3Measurement precision
If biomarkers are detected and quantified to identify individuals at risk for BOS, then early and accurate diagnosis is enabled, but the complexity of the diagnostic system increases
Solution Approach 1:
The patent segments the diagnostic approach into distinct components: detection of specific biomarkers (ILK, KLHL5, KID, SAC3D1, PRP12, ATP13A1, SNX8, CASP8AP2, and complement components), quantification of biomarker levels, comparison to control values, and risk assessment. This segmentation allows each component to be optimized independently and facilitates implementation through standardized assays and algorithms.
Solution Approach 2:
The patent changes the diagnostic parameter from mechanical lung function measurements to biochemical biomarker concentrations. By detecting and quantifying specific proteins and molecules in blood or other biological samples, the system transforms the diagnostic basis from physical measurements requiring patient coordination to biochemical assays that can be performed on simple blood samples, thereby reducing overall system complexity despite the advanced nature of biomarker detection.
Data Source
AI summary
Disclosed are methods for treating an individual at risk for developing bronchiolitis obliterans syndrome (BOS) after hematopoietic stem cell transplant (HSCT), comprising a) detecting a biomarker; b) quantifying a biomarker level; and c) comparing the level of a biomarker to a control value; wherein a deviation in a level of biomarker indicates that said individual is likely to develop the lung condition.