Gene therapy for epilepsy


Epilepsy is a devastating disorder which affects about 1.5 to 3 million people in the United States (about 0.5%–1.0% of the population), and as many as 50 million worldwide. Antiepileptic drugs (AEDs) can successfully treat about 2/3 of epileptic patients (Nadkarni et al. 2005). Thus, many patients are left with intractable seizures, with surgery as a possible last resort. The source of epilepsy is sometimes thought to be an intracerebral imbalance between excitation and inhibitory neurotransmission. A major excitatory neurotransmitter is glutamate, and a key inhibitory neurotransmitter is GABA. Most AEDs have a mode of action directed at one or the other of these neural processes. A more generalized effect on neural excitation and inhibition is caused by neuropeptide compounds (Hokfelt 1991). In the human, precursors of neuropeptides are encoded by several dozen genes. Consequently, one potential mechanism for modulating epileptic seizures is gene therapy, in which genes are inserted directly into the cells. A common method for implementing gene therapy is through viral vectors that deliver modified genes to produce proteins and enzymes. In the case of epilepsy, the goal of viral vectors is to increase the intracerebral production of inhibitory products, which may be particularly beneficial because of the large variety of etiologic epilepsies. With adeno-associated viral vectors (AAVs), the approach is to transfer the appropriate modified gene into the infected cell, resulting in the expression of gene products. AAVs have been used frequently for treatment of numerous conditions. This vector has low immunogenicity with success in delivery of potential treatment forms to non dividing neurons. In addition, inflammation is low, and AAV vectors are long acting. The approach of gene therapy via viral vectors has been fairly well researched. For example, this method has been used to attempt treatment of certain muscle and eye diseases in humans (Boison 2007). In animals, various successful treatments have been demonstrated in Gunn rats (a model of the Crigler-Najjar Syndrome, with hyperbilirubinemia). In particular, gene therapy has served to provide Gunn rats with enough bilirubin conjugation enzyme to essentially eliminate jaundice. This effect has been achieved in one treatment which served the life span of the rat (2 years). This treatment should be soon ready for clinical trials (McCandless 2011).

DOI: 10.1007/s11011-010-9209-7

Cite this paper

@article{Mccandless2010GeneTF, title={Gene therapy for epilepsy}, author={D W Mccandless and Jeffrey McCandless}, journal={Metabolic Brain Disease}, year={2010}, volume={25}, pages={363-366} }