Alpha-Synuclein Transcript Biomarkers for Lewy Bodies Diagnosis
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Solution Overview
Problem
Current methods for diagnosing synucleinopathies, such as Parkinson's disease and Dementia with Lewy bodies, are inadequate for early and accurate differential diagnosis, leading to misdiagnosis and ineffective treatment, as they rely on invasive and costly neuroimaging techniques or unreliable biomarkers that require aggregate forms of alpha-synuclein proteins, which are not present in early stages of the disease.
Innovation Solution
The use of specific transcripts (SNCAtv2 and SNCAtv3) of the alpha-synuclein gene as biomarkers in human biological fluids for in vitro diagnosis, allowing for early detection and differential diagnosis of synucleinopathies by quantifying these transcripts using techniques like quantitative real-time PCR, providing a non-invasive and cost-effective method.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If neuroimaging techniques (DaTscan) are used for diagnosis, then diagnostic capability is improved, but cost-effectiveness deteriorates and accessibility worsens due to radioactive compounds and limited availability
Solution Approach 1:
The patent replaces expensive, limited-access neuroimaging with a cheap, disposable biomarker test using alpha-synuclein transcripts in blood samples. This single-use molecular test provides equivalent diagnostic information without requiring expensive imaging equipment or radioactive materials, making the diagnosis accessible and cost-effective while maintaining reliability
2Reliability
If aggregate forms of alpha-synuclein protein are used as biomarkers, then synucleinopathy detection is improved, but early diagnosis capability deteriorates because aggregates are not present in early stages
Solution Approach 1:
The patent detects alpha-synuclein transcripts (mRNA) which are present before protein aggregation occurs. By measuring the genetic transcript level early in the disease process, the test enables preliminary detection and diagnosis before the pathological aggregates form, allowing for early intervention while maintaining reliable synucleinopathy detection
Solution Approach 2:
The patent uses alpha-synuclein transcripts as an intermediary biomarker that bridges the gap between early disease onset and later aggregate formation. These transcripts serve as a measurable intermediate that indicates disease presence before the final pathological aggregates appear, enabling early diagnosis without waiting for aggregate formation
3Adaptability or versatility
If clinical overlap symptoms are used for differential diagnosis, then diagnostic scope is improved, but diagnostic accuracy deteriorates due to indistinguishable symptoms between PD and DLB
Solution Approach 1:
The patent extracts the diagnostic information from shared clinical symptoms and isolates it in a specific molecular marker - the alpha-synuclein transcript level. By measuring this specific biomarker in blood samples, the test distinguishes between PD and DLB patients who present with overlapping symptoms, maintaining broad diagnostic scope while achieving high diagnostic accuracy through objective molecular measurement
Data Source
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AI summary
The present invention provides a method for the in vitro diagnosis of dementia with Lewy bodies in a human patient comprising the step of determining the amount of transcripts SNCAtv3 (SEQ ID NO: 3) and SNCAtv2 (SEQ ID NO: 2) of the human alpha-synuclein gene (SNCA) in a biological sample obtained from the patient, wherein when the amount of both transcripts determined for the patient is reduced with respect to a reference value, this is indicative of the presence of dementia with Lewy bodies in the patient. The invention further provides means to determine the amount of said transcripts, as well as a method to stablish the response of a patient which has been diagnosed with dementia with Lewy bodies to a medical regime for its treatment by determining the amount of transcripts SNCAtv3 and SNCAtv2 in a biological sample from the patient before and after the treatment.