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Unilateral ex vivo gene therapy by GDNF in epileptic rats


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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We thank Susanne Jonsson and Nora Pernaa for performing the immunohistochemistry.


This work received financial support by the European Commission, FP7-PEOPLE-2011-IAPP, project 285827.

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Correspondence to Merab Kokaia.

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LW is the scientific founder of NsGene A/S, and an employee of the company with minor share ownership. The remaining authors declare that they have no conflict of interest.

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Nanobashvili, A., Melin, E., Emerich, D. et al. Unilateral ex vivo gene therapy by GDNF in epileptic rats. Gene Ther 26, 65–74 (2019).

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