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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Julia Alicja Szczygieł
  • Kira Iben Danielsen
  • Esbjörn Melin
  • Søren Hofman Rosenkranz
  • Stanislava Pankratova
  • Annika Ericsson
  • Karin Agerman
  • Merab Kokaia
  • David Paul Drucker Woldbye
Organisations
External organisations
  • University of Copenhagen
  • Skåne University Hospital
  • CombiGene AB
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences

Keywords

  • AAV viral vector, gene therapy, hippocampus, learning and memory, NPY, Y2
Original languageEnglish
Article number232
JournalFrontiers in Molecular Neuroscience
Volume13
Publication statusPublished - 2020
Publication categoryResearch
Peer-reviewedYes