RAN Protein Detection for Reliable Huntington's Disease Diagnosis
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Solution Overview
Problem
Current diagnostic methods for Huntington's disease (HD) are limited in their ability to reliably detect the presence of disease-associated proteins, and existing therapies do not provide a cure.
Innovation Solution
The detection of repeat-associated non-ATG (RAN) proteins, such as poly-Alanine, poly-Serine, and poly-Cysteine, in biological samples like blood and cerebrospinal fluid, using antigen retrieval techniques, followed by immunoblot analysis or ELISA, to diagnose HD, and the use of antisense oligonucleotides or antibodies to treat the disease.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional diagnostic methods are used to detect Huntington's disease, then the diagnostic process is simple, but the detection reliability and measurement precision are insufficient
Solution Approach 1:
The patent applies preliminary action by performing antigen retrieval treatment before detecting RAN proteins in biological samples. This预处理 step involves treating the sample with agents such as proteases, detergents, or heat to unmask epitopes that would otherwise be inaccessible, thereby improving detection reliability without adding complex instrumentation
Solution Approach 2:
The patent uses antibodies as intermediary molecules to detect RAN proteins in biological samples. The antibodies specifically bind to RAN proteins, enabling indirect detection that enhances measurement precision and reliability while maintaining relatively simple diagnostic procedures through standard immunoassay techniques
2Measurement precision
If antigen retrieval techniques are applied to detect RAN proteins, then measurement precision and detection reliability improve, but the diagnostic process becomes more complex and time-consuming
Solution Approach 1:
The patent applies partial action by using targeted antigen retrieval methods that focus specifically on unmasking RAN protein epitopes rather than comprehensive sample processing. This selective approach achieves sufficient detection precision while minimizing unnecessary time consumption through optimized and focused retrieval protocols
3Loss of information
If genetic testing is used to identify mutant Htt, then the presence of disease-causing mutation can be determined, but this does not indicate initiation of pathogenic process or provide prognostic information
Solution Approach 1:
The patent extracts and detects specific RAN proteins (poly-Alanine, poly-Serine, poly-Cysteine) from biological samples as biomarkers that indicate active pathogenic processes. This extraction of specific protein markers from complex biological samples provides functional information about disease progression without requiring complex multi-parameter analysis systems
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
Provides a reliable method for diagnosing HD by detecting RAN proteins reproducibly and offers therapeutic options to target these proteins, potentially slowing or halting disease progression.
Implementation Method 1
detecting in a biological sample obtained from a subject at least one RAN protein... wherein the RAN protein is not polyGln; diagnosing the subject as having Huntington's disease based upon the presence of the at least one RAN protein
Implementation Method 2
In some embodiments, the antigen retrieval method is heat-induced epitope retrieval (HIER)
Implementation Method 3
In some embodiments, the antigen retrieval method comprises protease-induced epitope retrieval (PIER)
Implementation Method 4
In some embodiments, an antigen retrieval method comprises formic acid treatment
Data Source
AI summary
The disclosure provides methods for the diagnosis of Huntington's disease. In some embodiments, the method comprises detecting one or more repeat associated non-ATG (RAN) proteins in a biological sample.