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

Szczygieł, Julia Alicja ; Danielsen, Kira Iben ; Melin, Esbjörn LU orcid ; Rosenkranz, Søren Hofman ; Pankratova, Stanislava ; Ericsson, Annika ; Agerman, Karin ; Kokaia, Merab LU and Woldbye, David Paul Drucker (2020) In Frontiers in Molecular Neuroscience 13.
Abstract

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... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
AAV viral vector, gene therapy, hippocampus, learning and memory, NPY, Y2
in
Frontiers in Molecular Neuroscience
volume
13
article number
232
publisher
Frontiers Media S. A.
external identifiers
  • pmid:33343295
  • scopus:85097814499
ISSN
1662-5099
DOI
10.3389/fnmol.2020.603409
language
English
LU publication?
yes
id
17753b5f-ea77-4d6a-87c1-1a07e980bbce
date added to LUP
2021-01-05 13:54:41
date last changed
2024-03-20 22:59:48
@article{17753b5f-ea77-4d6a-87c1-1a07e980bbce,
  abstract     = {{<p>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.</p>}},
  author       = {{Szczygieł, Julia Alicja and Danielsen, Kira Iben and Melin, Esbjörn and Rosenkranz, Søren Hofman and Pankratova, Stanislava and Ericsson, Annika and Agerman, Karin and Kokaia, Merab and Woldbye, David Paul Drucker}},
  issn         = {{1662-5099}},
  keywords     = {{AAV viral vector; gene therapy; hippocampus; learning and memory; NPY; Y2}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Molecular Neuroscience}},
  title        = {{Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy : Preclinical Data in Rats}},
  url          = {{http://dx.doi.org/10.3389/fnmol.2020.603409}},
  doi          = {{10.3389/fnmol.2020.603409}},
  volume       = {{13}},
  year         = {{2020}},
}