Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy: Preclinical Data in Rats
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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; Rosenkranz, Søren Hofman; Pankratova, Stanislava; Ericsson, Annika; Agerman, Karin; Kokaia, Merab; Woldbye, David Paul Drucker.
In: Frontiers in Molecular Neuroscience, Vol. 13, 232, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy
T2 - Preclinical Data in Rats
AU - Szczygieł, Julia Alicja
AU - Danielsen, Kira Iben
AU - Melin, Esbjörn
AU - Rosenkranz, Søren Hofman
AU - Pankratova, Stanislava
AU - Ericsson, Annika
AU - Agerman, Karin
AU - Kokaia, Merab
AU - Woldbye, David Paul Drucker
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
KW - AAV viral vector
KW - gene therapy
KW - hippocampus
KW - learning and memory
KW - NPY
KW - Y2
U2 - 10.3389/fnmol.2020.603409
DO - 10.3389/fnmol.2020.603409
M3 - Journal article
C2 - 33343295
AN - SCOPUS:85097814499
VL - 13
JO - Frontiers in Molecular Neuroscience
JF - Frontiers in Molecular Neuroscience
SN - 1662-5099
M1 - 232
ER -
ID: 253780219