Invention:
The leukocyte gene biomarkers presented here identify totally new and different genes whose expression predict temporal lobe epilepsy (TLE) seizure frequency. This seizure frequency prediction is a manifestation of the underlying pathophysiology of TLE disease states which have, heretofore, not been identified to have a dichotomized genetic basis. Targeting the underlying TLE pathophysiology in a personalized, therapeutic manner, based on leukocyte gene expression, represents a new medical decision-making paradigm, amenable to pharmacologic treatment and surgical therapy. The dichotomized approach will more appropriately target therapy to the genetic and biological pathway TLE abnormalities amenable to treatment intervention.
Background:
High and low seizure frequency categories of intractable TLE represent two mechanistically different disease states, based on leukocyte gene expression. These newly identified leukocyte gene biomarkers, for high and low seizure frequency, may direct medical management of TLE by identifying those biological pathways and genes which are involved in the pathophysiology of individual categories of TLE, high and low seizure frequency. These newly identified leukocyte gene and biological pathway biomarkers could direct personalized medical management of intractable TLE with anti-seizure medication targeting the specific gene and biologic pathways, which are unique to high and low seizure frequency categories of disease. In addition, these newly identified leukocyte gene and biological pathway biomarkers could direct personalized surgical intervention, including vagus nerve stimulation, deep brain stimulation of the anterior nucleus of the thalamus, responsive neurostimulation and emerging techniques of stem cell and gene therapy in temporal lobe epilepsy.
Currently, medical management of intractable TLE is based on the clinical diagnosis of intractable TLE. A more tailored approach for TLE treatment, based on mechanistically separate categories of disease of high and low seizure frequency, will allow more personalized pharmacologic therapy directed at TLE genomic and biological pathway-specific pathophysiology for the high and low seizure frequency categories of disease. This more personalized genomic-based therapy should produce improved control of temporal lobe epilepsy, including reduced seizure frequency.
Applications:
- Direct personalized surgical intervention
- Utilized in emerging techniques of stem cell and gene therapy
Advantages:
- New medical decision-making paradigm
- More appropriately target therapy to TLE abnormalities (more personalized)
- Improved control of TLE
