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Gene Therapy Vector...
Gene Therapy Vector Encoding Neuropeptide Y and Its Receptor Y2 for Future Treatment of Epilepsy : Preclinical Data in Rats
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- Szczygieł, Julia Alicja (author)
- University of Copenhagen
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- Danielsen, Kira Iben (author)
- University of Copenhagen,Skåne University Hospital
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- Melin, Esbjörn (author)
- Lund University,Lunds universitet,Experimentell Epilepsi,Forskargrupper vid Lunds universitet,Experimental Epilepsy Group,Lund University Research Groups,Skåne University Hospital
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- Rosenkranz, Søren Hofman (author)
- University of Copenhagen
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- Pankratova, Stanislava (author)
- University of Copenhagen
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- Ericsson, Annika (author)
- CombiGene AB
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- Agerman, Karin (author)
- CombiGene AB
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- Kokaia, Merab (author)
- Lund University,Lunds universitet,Experimentell Epilepsi,Forskargrupper vid Lunds universitet,Experimental Epilepsy Group,Lund University Research Groups,Skåne University Hospital
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- Woldbye, David Paul Drucker (author)
- University of Copenhagen
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(creator_code:org_t)
- 2020-12-04
- 2020
- English.
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In: Frontiers in Molecular Neuroscience. - : Frontiers Media SA. - 1662-5099. ; 13
- Related links:
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http://dx.doi.org/10... (free)
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https://www.frontier...
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https://lup.lub.lu.s...
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https://doi.org/10.3...
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
Keyword
- AAV viral vector
- gene therapy
- hippocampus
- learning and memory
- NPY
- Y2
Publication and Content Type
- art (subject category)
- ref (subject category)
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