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Unilateral ex vivo gene therapy by GDNF in epileptic rats.
- Source :
-
Gene therapy [Gene Ther] 2019 Apr; Vol. 26 (3-4), pp. 65-74. Date of Electronic Publication: 2018 Nov 21. - Publication Year :
- 2019
-
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 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.
- Subjects :
- Animals
Anticonvulsants pharmacology
Brain metabolism
Disease Models, Animal
Epilepsy genetics
Epilepsy physiopathology
Epilepsy therapy
Epilepsy, Temporal Lobe therapy
Glial Cell Line-Derived Neurotrophic Factor genetics
Hippocampus metabolism
Male
Neurons metabolism
Rats
Rats, Wistar
Seizures genetics
Genetic Therapy methods
Glial Cell Line-Derived Neurotrophic Factor therapeutic use
Seizures therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1476-5462
- Volume :
- 26
- Issue :
- 3-4
- Database :
- MEDLINE
- Journal :
- Gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 30464254
- Full Text :
- https://doi.org/10.1038/s41434-018-0050-7