Direct gene transfer into human epileptogenic hippocampal tissue with an adeno-associated virus vector: implications for a gene therapy approach to epilepsy.
| Publication Type | Academic Article |
| Authors | Freese A, Kaplitt M, O'Connor W, Abbey M, Langer D, Leone P, O'Connor M, During M |
| Journal | Epilepsia |
| Volume | 38 |
| Issue | 7 |
| Pagination | 759-66 |
| Date Published | 07/01/1997 |
| ISSN | 0013-9580 |
| Keywords | Dependovirus, Epilepsy, Gene Transfer Techniques, Genetic Therapy, Hippocampus |
| Abstract | PURPOSE: Virus vectors capable of transferring genetic information into human cells provide hope for improved therapy in several neurological diseases, including epilepsy. We evaluated the ability of an adeno-associated virus (AAV) vector to transfer and cause expression of a lacZ marker gene in brain slices obtained from patients undergoing temporal lobectomy for control of medically intractable seizures. METHODS: Human brain slices were injected with an AAV vector (AAVlacZ) encoding Escherichia coli beta-galactosidase and incubated for as long as 24 h. The presence of lacZ mRNA. beta-galactosidase protein and enzymatic activity were assayed by reverse transcriptase polymerase chain reaction (rtPCR), immunocytochemistry, and the X-Gal technique, respectively. RESULTS: AAVlacZ directed the expression in human epileptogenic brain of E. coli beta-galactosidase that had functional activity. Expression was observed in < or =5 h and was sustained for as long as the slices were viable. Morphological analysis indicated that neurons were preferentially transfected, and there was no evidence of cytotoxicity. CONCLUSIONS: Our results confirm the feasibility of using AAV vectors to transfer genes into the human CNS and in particular, into neurons. Replacement of the lacZ gene with a functional gene modulating hippocampal neuronal physiology, might allow a localized genetic intervention for focal seizures based on the stereotaxic or endovascular delivery of such a vector system into the appropriate brain region. |
| DOI | 10.1111/j.1528-1157.1997.tb01462.x |
| PubMed ID | 9579902 |