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Drug resistance in epilepsy: human epilepsy.
S M Sisodiya1, W R Lint, B N Harding
1University Department of Clinical Neurology, Institute of Neurology, University College London, UK.
Novartis Foundation Symposium
|May 7, 2002
Summary
Drug resistance proteins like P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) are expressed in brain tissue from epilepsy patients. This suggests their potential role in refractory epilepsy drug resistance.
Area of Science:
- Neuroscience
- Pharmacology
- Oncology
Background:
- The mechanisms underlying drug resistance in human epilepsy remain unclear.
- Drug resistance in cancer shares similarities, suggesting a role for drug resistance proteins.
Purpose of the Study:
- To investigate the potential role of drug resistance proteins in refractory epilepsy.
- To examine the expression of P glycoprotein (Pgp) and multidrug resistance-associated protein 1 (MRP1) in human brain tissue associated with epilepsy.
Main Methods:
- Immunohistochemistry was used to detect Pgp and MRP1 expression.
- Human brain tissue samples from epilepsy cases (malformation of cortical development, hippocampal sclerosis, dysembryoplastic neuroepithelial tumours) and controls were analyzed.
Main Results:
- Pgp and MRP1 were expressed in glia in various epilepsy-associated pathologies.
- Dysplastic neurons also showed MRP1 expression in a specific malformation type.
- Overexpression was often concentrated around blood vessels.
- Expression patterns suggest some pathologies may have constitutive Pgp and MRP1 expression.
Conclusions:
- The findings suggest that drug resistance proteins, Pgp and MRP1, may contribute to the development of drug resistance in refractory epilepsy.
- Further research is warranted to elucidate the precise role of these proteins in epilepsy treatment.