RNA Marker Panel Predicts Drug-Resistant Epilepsy in Tuberous Sclerosis
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Solution Overview
Problem
Current methods lack molecular markers for predicting whether epilepsy in tuberous sclerosis patients will be drug-resistant, leading to inadequate early intervention and increased risk of intellectual disability.
Innovation Solution
A panel of RNA markers, including GLV1-40, IGVK4-1, IGLC7, IGLV3-19, IGHV4-34, IGKV1-39, IGHV6-1, IGHV1-3, IGHV3-53, IGKV3-15, TNFRSF13B, and IGLJ2, is used to predict drug-resistant epilepsy in girls aged up to 24 months with tuberous sclerosis, with measurement via qRT-PCR, ddPCR, or next-generation sequencing, allowing for early identification before the onset of seizures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of time
If standard epilepsy treatment is initiated after first seizure, then treatment can be started, but the risk of intellectual disability increases due to delayed intervention
Solution Approach 1:
The patent applies preliminary action by measuring RNA marker expression levels in patients with TSC before they experience their first epileptic seizure. This allows clinicians to identify high-risk patients and initiate antiepileptic treatment prophylactically, before seizures occur, thereby preventing the development of epilepsy and associated intellectual disability risks.
Solution Approach 2:
The patent applies preliminary anti-action by using the RNA marker panel to predict which patients are at high risk of developing drug-resistant epilepsy, and initiating treatment in advance to counteract the harmful effects before they manifest. This preemptive approach opposes the natural progression toward drug-resistant epilepsy and intellectual disability.
2Measurement precision
If RNA marker panel measurement is implemented, then early prediction of drug-resistant epilepsy is achieved, but diagnostic complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the complex diagnostic task into two parts: first, measuring the expression levels of multiple specific RNA markers (IGLV1-40, IGVK4-1, IGLC7, IGLV3-19, IGHV4-34, IGKV1-39, IGHV6-1, IGHV1-3, IGHV3-53, IGKV3-15, TNFRSF13B, IGLJ2) using established qRT-PCR technology; second, comparing the measured levels against established thresholds to determine high-risk status. This segmentation makes the complex diagnostic process more manageable and implementable.
3Reliability
If multiple RNA markers are measured, then prediction reliability improves, but measurement time and resource requirements increase
Solution Approach 1:
The patent applies merging by combining the measurement of multiple RNA markers into a single integrated qRT-PCR assay. All twelve markers (IGLV1-40, IGVK4-1, IGLC7, IGLV3-19, IGHV4-34, IGKV1-39, IGHV6-1, IGHV1-3, IGHV3-53, IGKV3-15, TNFRSF13B, IGLJ2) are measured simultaneously in one test, rather than requiring separate measurements for each marker, thereby maintaining high prediction reliability while minimizing measurement time.
Data Source
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AI summary
The subject of invention is a panel of RNA markers for the prediction of epilepsy, in particular drug resistant epilepsy, in girls aged up to 24 months with tuberous sclerosis, characterised in that it comprises the following markers GLV1-40, IGVK4-1, IGLC7, IGLV3-19, IGHV4-34, IGKV1-39, IGHV6-1, IGHV1-3, IGHV3-53, IGKV3-15, TNFRSF13B, IGLJ2. Another subject of invention is an in vitro method for the prediction of epilepsy, in particular drug-resistant epilepsy, in girls aged up to 24 months with tuberous sclerosis, comprising the steps of: a) Measurement of the expression level of at least one marker; b) Determination of the risk of epilepsy, in particular drug-resistant epilepsy, based on the expression level of at least one marker, characterized in that said at least one marker is an RNA marker belonging to the panel of predictive markers according to invention, which comprises IGLV1-40, IGVK4-1, IGLC7, IGLV3-19, IGHV4-34, IGKV1-39, IGHV6-1, IGHV1-3, IGHV3-53, IGKV3-15, TNFRSF13B, IGLJ2, wherein the prediction of the occurrence of drug-resistant epilepsy is based on a reduced expression level of said at least one marker compared to a reference level, wherein the prediction of drug-controlled epilepsy is based on elevated expression level of at least one marker compared to reference level; whereby in step (a) the expression level of at least one marker is measured before the first epileptic seizure occurs. Another subject of invention is an use of the marker panel according to invention, in the prediction of the occurrence of epilepsy, in particular drug-resistant epilepsy, in girls aged up to 24 months with tuberous sclerosis before the occurrence of epileptic seizures according to the method according to invention.