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Unilateral ex vivo gene therapy by GDNF in epileptic rats

Gene Therapy volume 26, pages 65–74 (2019)Cite this article

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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.

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Acknowledgements

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

Funding

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

Author information

Author notes

  1. These authors contributed equally: Avtandil Nanobashvili and Esbjörn Melin.

Authors and Affiliations

  1. NsGene A/S, Ballerup, Denmark

    Avtandil Nanobashvili & Jens Tornøe

  2. Epilepsy Centre, Department of Clinical Sciences, Lund University Hospital, Lund, Sweden

    Esbjörn Melin & Merab Kokaia

  3. NsGene, Inc, Providence, RI, USA

    Dwaine Emerich & Lars Wahlberg

  4. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Michele Simonato

  5. Division of Neuroscience, University Vita-Salute San Raffaele, Milan, Italy

    Michele Simonato

Authors
  1. Avtandil Nanobashvili
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  3. Dwaine Emerich
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  4. Jens Tornøe
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  5. Michele Simonato
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  6. Lars Wahlberg
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  7. Merab Kokaia
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Correspondence to Merab Kokaia.

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Conflict of interest

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). https://doi.org/10.1038/s41434-018-0050-7

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