Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy: Preclinical Data in Rats

Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy: Preclinical Data in Rats

Gene therapy to treat pharmacoresistant temporal lobe epilepsy in humans is now being developed using an AAV vector (CG01) that encodes the combination of neuropeptide Y and its antiepileptic receptor Y2. With this in mind, the present study aimed to provide important preclinical data on the effects...

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Published in:Frontiers in molecular neuroscience Vol. 13; p. 232
Main Authors: Szczygieł, Julia Alicja, Danielsen, Kira Iben, Melin, Esbjörn, Rosenkranz, Søren Hofman, Pankratova, Stanislava, Ericsson, Annika, Agerman, Karin, Kokaia, Merab, Woldbye, David Paul Drucker
Format: Journal Article
Language:English
Published: Switzerland Frontiers Research Foundation 04-12-2020
Frontiers Media S.A
Subjects:
AAV viral vector
Astrocytes
Basic Medicine
Body weight
Cognitive ability
Convulsions & seizures
Design of experiments
Epilepsy
Gene therapy
Hippocampus
Laboratory animals
learning and memory
Long term memory
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Neuropeptide Y
Neuropeptides
Neuroscience
Neurosciences
Neurovetenskaper
NPY
Oligodendrocytes
Proteins
Rodents
Side effects
Surgery
Temporal lobe
Transgenes
Tropism
Vectors (Biology)
Sweden
Y2
gene therapy
hippocampus
learning and memory
NPY
AAV viral vector
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Summary:Gene therapy to treat pharmacoresistant temporal lobe epilepsy in humans is now being developed using an AAV vector (CG01) that encodes the combination of neuropeptide Y and its antiepileptic receptor Y2. With this in mind, the present study aimed to provide important preclinical data on the effects of CG01 on the duration of transgene expression, cellular tropism, and potential side effects on body weight and cognitive function. The CG01 vector was administered unilaterally into the dorsal and ventral hippocampus of adult male rats and expression of both transgenes was found to remain elevated without a sign of decline at 6 months post-injection. CG01 appeared to mediate expression selectively in hippocampal neurons, without expression in astrocytes or oligodendrocytes. No effects were seen on body weight as well as on short- or long-term memory as revealed by testing in the Y-maze or Morris water maze tests. Thus these data show that unilateral CG01 vector treatment as future gene therapy in pharmacoresistant temporal lobe epilepsy patients should result in stable and long-term expression predominantly in neurons and be well tolerated without side effects on body weight and cognitive function.
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Reviewed by: Richard Kovacs, Charité—Universitätsmedizin Berlin, Germany; Andreas Draguhn, Heidelberg University, Germany; Adam Strzelczyk, University Hospital Frankfurt, Germany
Edited by: Oliver von Bohlen und Halbach, Universitätsmedizin Greifswald, Germany
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2020.603409