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Unilateral ex vivo gene therapy by GDNF in epileptic rats

Nanobashvili, Avtandil LU ; Melin, Esbjörn LU ; Emerich, Dwaine; Tornøe, Jens; Simonato, Michele; Wahlberg, Lars and Kokaia, Merab LU (2019) In Gene Therapy 26(3-4). p.65-74
Abstract

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. This neurological disorder is characterized by focal seizures originating in the temporal lobe, often with secondary generalization. A variety of pharmacological treatments exist for patients suffering from focal seizures, but systemically administered drugs offer only symptomatic relief and frequently cause unwanted side effects. Moreover, available drugs are ineffective in one third of the epilepsy patients. Thus, developing more targeted and effective treatment strategies for focal seizures, originating from, e.g., the temporal lobe, is highly warranted. In order to deliver potential anti-epileptic agents directly into the seizure focus we used encapsulated... (More)

Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. This neurological disorder is characterized by focal seizures originating in the temporal lobe, often with secondary generalization. A variety of pharmacological treatments exist for patients suffering from focal seizures, but systemically administered drugs offer only symptomatic relief and frequently cause unwanted side effects. Moreover, available drugs are ineffective in one third of the epilepsy patients. Thus, developing more targeted and effective treatment strategies for focal seizures, originating from, e.g., the temporal lobe, is highly warranted. In order to deliver potential anti-epileptic agents directly into the seizure focus we used encapsulated cell biodelivery (ECB), a specific type of ex vivo gene therapy. Specifically, we asked whether unilateral delivery of glial cell line-derived neurotrophic factor (GDNF), exclusively into the epileptic focus, would suppress already established spontaneous recurrent seizures (SRS) in rats. Our results show that GDNF delivered by ECB devices unilaterally into the seizure focus in the hippocampus effectively decreases the number of SRS in epileptic rats. Thus, our study demonstrates that focal unilateral delivery of neurotrophic factors, such as GDNF, using ex vivo gene therapy based on ECB devices could be an effective anti-epileptic strategy providing a bases for the development of a novel, alternative, treatment for focal epilepsies.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Gene Therapy
volume
26
issue
3-4
pages
65 - 74
publisher
Nature Publishing Group
external identifiers
  • scopus:85056860787
ISSN
0969-7128
DOI
10.1038/s41434-018-0050-7
language
English
LU publication?
yes
id
64269a59-1109-468a-af42-236908c298a8
date added to LUP
2018-11-30 08:45:55
date last changed
2019-10-15 06:51:53
@article{64269a59-1109-468a-af42-236908c298a8,
  abstract     = {<p>Temporal lobe epilepsy (TLE) is the most common type of epilepsy in adults. This neurological disorder is characterized by focal seizures originating in the temporal lobe, often with secondary generalization. A variety of pharmacological treatments exist for patients suffering from focal seizures, but systemically administered drugs offer only symptomatic relief and frequently cause unwanted side effects. Moreover, available drugs are ineffective in one third of the epilepsy patients. Thus, developing more targeted and effective treatment strategies for focal seizures, originating from, e.g., the temporal lobe, is highly warranted. In order to deliver potential anti-epileptic agents directly into the seizure focus we used encapsulated cell biodelivery (ECB), a specific type of ex vivo gene therapy. Specifically, we asked whether unilateral delivery of glial cell line-derived neurotrophic factor (GDNF), exclusively into the epileptic focus, would suppress already established spontaneous recurrent seizures (SRS) in rats. Our results show that GDNF delivered by ECB devices unilaterally into the seizure focus in the hippocampus effectively decreases the number of SRS in epileptic rats. Thus, our study demonstrates that focal unilateral delivery of neurotrophic factors, such as GDNF, using ex vivo gene therapy based on ECB devices could be an effective anti-epileptic strategy providing a bases for the development of a novel, alternative, treatment for focal epilepsies.</p>},
  author       = {Nanobashvili, Avtandil and Melin, Esbjörn and Emerich, Dwaine and Tornøe, Jens and Simonato, Michele and Wahlberg, Lars and Kokaia, Merab},
  issn         = {0969-7128},
  language     = {eng},
  number       = {3-4},
  pages        = {65--74},
  publisher    = {Nature Publishing Group},
  series       = {Gene Therapy},
  title        = {Unilateral ex vivo gene therapy by GDNF in epileptic rats},
  url          = {http://dx.doi.org/10.1038/s41434-018-0050-7},
  volume       = {26},
  year         = {2019},
}