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GDNF released from encapsulated cells suppresses seizure activity in the epileptic hippocampus.

Kanter Schlifke, Irene LU ; Fjord-Larsen, Lone; Kusk, Philip; Ängehagen, Mikael LU ; Wahlberg, Lars and Kokaia, Merab LU (2009) In Experimental Neurology 216. p.413-419
Abstract
To date, a variety of pharmacological treatments exists for patients suffering epilepsy, but systemically administered drugs offer only symptomatic relief and often cause unwanted side effects. Moreover, available drugs are not effective in one third of the patients. Thus, more local and more effective treatment strategies need to be developed. Gene therapy-based expression of endogenous anti-epileptic agents represents a novel approach that could interfere with the disease process and result in stable and long-term suppression of seizures in epilepsy patients. We have reported earlier that direct in vivo viral vector-mediated overexpression of the glial cell line-derived neurotrophic factor (GDNF) in the rat hippocampus suppressed... (More)
To date, a variety of pharmacological treatments exists for patients suffering epilepsy, but systemically administered drugs offer only symptomatic relief and often cause unwanted side effects. Moreover, available drugs are not effective in one third of the patients. Thus, more local and more effective treatment strategies need to be developed. Gene therapy-based expression of endogenous anti-epileptic agents represents a novel approach that could interfere with the disease process and result in stable and long-term suppression of seizures in epilepsy patients. We have reported earlier that direct in vivo viral vector-mediated overexpression of the glial cell line-derived neurotrophic factor (GDNF) in the rat hippocampus suppressed seizures in different animal models of epilepsy. Here we explored whether transplantation of encapsulated cells that release GDNF in the hippocampus could also exert a seizure-suppressant effect. Such ex vivo gene therapy approach represents a novel, more clinically safe approach, since the treatment could be terminated by retrieving the transplants from the brain. We demonstrate here that encapsulated cells, which are genetically modified to produce and release GDNF, can suppress recurrent generalized seizures when implanted into the hippocampus of kindled rats. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Experimental Neurology
volume
216
pages
413 - 419
publisher
Academic Press
external identifiers
  • wos:000264606600022
  • pmid:19162016
  • scopus:62349124875
ISSN
0014-4886
DOI
10.1016/j.expneurol.2008.12.021
language
English
LU publication?
yes
id
7954a323-2df6-479e-a898-fbc5527974d7 (old id 1289375)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/19162016?dopt=Abstract
date added to LUP
2009-02-04 12:27:56
date last changed
2017-07-30 04:49:02
@article{7954a323-2df6-479e-a898-fbc5527974d7,
  abstract     = {To date, a variety of pharmacological treatments exists for patients suffering epilepsy, but systemically administered drugs offer only symptomatic relief and often cause unwanted side effects. Moreover, available drugs are not effective in one third of the patients. Thus, more local and more effective treatment strategies need to be developed. Gene therapy-based expression of endogenous anti-epileptic agents represents a novel approach that could interfere with the disease process and result in stable and long-term suppression of seizures in epilepsy patients. We have reported earlier that direct in vivo viral vector-mediated overexpression of the glial cell line-derived neurotrophic factor (GDNF) in the rat hippocampus suppressed seizures in different animal models of epilepsy. Here we explored whether transplantation of encapsulated cells that release GDNF in the hippocampus could also exert a seizure-suppressant effect. Such ex vivo gene therapy approach represents a novel, more clinically safe approach, since the treatment could be terminated by retrieving the transplants from the brain. We demonstrate here that encapsulated cells, which are genetically modified to produce and release GDNF, can suppress recurrent generalized seizures when implanted into the hippocampus of kindled rats.},
  author       = {Kanter Schlifke, Irene and Fjord-Larsen, Lone and Kusk, Philip and Ängehagen, Mikael and Wahlberg, Lars and Kokaia, Merab},
  issn         = {0014-4886},
  language     = {eng},
  pages        = {413--419},
  publisher    = {Academic Press},
  series       = {Experimental Neurology},
  title        = {GDNF released from encapsulated cells suppresses seizure activity in the epileptic hippocampus.},
  url          = {http://dx.doi.org/10.1016/j.expneurol.2008.12.021},
  volume       = {216},
  year         = {2009},
}