PRECISION MEDICINE IN EPILEPSY: A GENDER-BASED OMICS APPROACH

Epilepsy is a complex neurological condition with recurrent seizures and is often
accompanied by cognitive impairments and varying drug responses. The recent advances in
precision medicine have highlighted the importance of proteomic and metabolomic
biomarkers in understanding the heterogeneity of the condition as well as the gender-related
differences in drug responses.Proteomic research has shown that there is differential
expression of synaptic and receptor-related proteins such as the GABA_A subunits,NMDA
receptor-associated proteins and synaptophysin, which are involved in the control of neuronal
excitability,synaptic plasticity,memory. Variations in the expression of drug transporter
proteins such as P-glycoprotein at the BBB have also been associated with reduced drug
penetration and pharmacoresistance in epilepsy patients.Metabolomic profiling has revealed
significant alterations in neurotransmitter and energy metabolism pathways, including
changes in glutamate,GABA, and lactate levels, which may influence seizure threshold and
cognitive function. In addition, inflammatory and neurotrophic biomarkers such as
may vary with sex hormones, contributing to gender-specific differences in disease
progression and drug response.Proteomic and metabolomic studies indicate gender
differences in epilepsy caused by certain sex hormones such as estrogen, progesterone,
testosterone, and a metabolite of progesterone named allopregnanolone. In females, estrogen
increases
NMDA receptor function and excitatory transmission, and
progesterone/allopregnanolone increases GABA_A receptor function, resulting in hormone
dependent modulation of seizure threshold and cognitive function. In males, testosterone and
its metabolites may modulate GABA_A and NMDA receptor function, resulting in distinct,
though relatively stable, receptor function compared with females. In addition, gender
differences in P-glycoprotein, a drug transporter involved in the BBB, might influence the
penetration of antiepileptic drugs.. These results demonstrate the relevance of hormone
dependent mechanisms in epilepsy and support the need of gender specific precision therapy
Keywords: Epilepsy, Proteomics, Metabolomics, Biomarkers, GABA, BDNF, P
glycoprotein, Pharmacoresistance, Precision medicine, Personalized therapy.