Autophagy-Deficient Trophoblast Cells for Protein Aggregate Detection
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Solution Overview
Problem
Current methods for detecting protein aggregates associated with neurodegenerative diseases like Alzheimer's and preeclampsia are invasive, costly, and lack sensitivity, requiring large plasma samples and complex procedures, while there is a need for a cost-effective, non-invasive blood test to detect these aggregates and treat related proteinopathies.
Innovation Solution
The use of autophagy-deficient trophoblast cells incubated with serum samples to detect protein aggregates using a protein aggregate dye, followed by staining and fluorescence detection, and the administration of trehalose to degrade these aggregates, which can be administered as a pharmaceutical composition to treat or prevent proteinopathies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to detect protein aggregates, then detection can be performed, but the methods are invasive, costly, and require large plasma samples with complex procedures
Solution Approach 1:
The patent uses an artificial cell system as an intermediary to detect protein aggregates. The artificial cells contain autophagy-deficient trophoblast cells that internalize protein aggregates from serum samples. This intermediary system simplifies the detection procedure while maintaining high sensitivity, as the cells naturally concentrate aggregates that can then be visualized using fluorescent dyes like ProteoStat
Solution Approach 2:
The patent replaces complex mechanical and chemical separation procedures with a biological uptake mechanism. Instead of using centrifugation, filtration, or chromatography to isolate protein aggregates, the system uses trophoblast cells to naturally internalize aggregates through their autophagy pathway, substituting mechanical separation with biological recognition and concentration
2Measurement precision
If current methods are used to detect protein aggregates, then detection can be performed, but large plasma samples are required
Solution Approach 1:
The patent applies local quality by concentrating protein aggregates into specific locations within the artificial cells. The autophagy-deficient trophoblast cells selectively internalize and accumulate protein aggregates in their cytoplasm, creating local concentrations that enhance detection sensitivity. This allows detection in minimal serum volumes (as low as 1-10 µL) because the aggregates are concentrated in the cellular compartments rather than being distributed throughout a large sample volume
3Reliability
If trehalose is administered to degrade protein aggregates, then proteinopathies may be ameliorated, but the mechanism and optimal dosing require establishment
Solution Approach 1:
The patent performs preliminary action by establishing the mechanism of trehalose-mediated protein aggregate degradation before clinical application. The artificial cell system is used to screen and validate trehalose and related compounds, determining their ability to degrade aggregates in a controlled in vitro setting. This preliminary validation in artificial cells provides a foundation for subsequent in vivo dosing studies, reducing the complexity of developing treatment protocols by pre-identifying effective compounds and mechanisms
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
This method allows for the sensitive detection of protein aggregates in serum samples using minimal volume, enabling early diagnosis of proteinopathies like Alzheimer's and preeclampsia, and promotes the degradation of protein aggregates, potentially ameliorating these conditions.
Implementation Method 1
staining the cells comprising at least one protein aggregate with a protein aggregate dye to provide stained cells; and detecting the at least one protein aggregate in the stained cells
Data Source
AI summary
The present disclosure relates in part to a blood-based method for the detection of a proteinopathy in a subject including, but not limited to, Alzheimer's disease (AD), mild cognitive impairment (MCI), and preeclampsia (PE), utilizing autophagy-deficient trophoblast (ADT) cells to sequester protein aggregates from the serum of said subject, and permit detection thereof. The present disclosure further relates to methods of treating, preventing, and/or ameliorating a proteinopathy in a subject by the administration of trehalose, a salt, solvate, stereoisomer, derivative, prodrug and or any mixture thereof.