Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury

Lior Molcho, Tali Ben-Zur, Yael Barhum, Ariel Angel, Mica Glat, Daniel Offen

Research output: Contribution to journalArticlepeer-review

Abstract

Research into stroke is driven by frustration over the limited available therapeutics. Targeting a single aspect of this multifactorial disease contributes to the therapeutic boundaries. To overcome this, we devised a novel multifactorial-cocktail treatment, using lentiviruses encoding excitatory amino acid transporter 2 (EAAT2(, glutamate dehydrogenase 2 (GDH2), and nuclear factor E2-related factor 2 (Nrf2) genes, that acts synergistically to address the effected excito-oxidative axis. Here, we used the vasoconstrictor endothelin-1 (ET-1) to induce focal ischemic injury in mice by direct injection into the striatum. Mice treated with the mixture of these three genes show significant improvement in body balance, motor coordination, and decreased motor asymmetry compared to each gene separately. These results demonstrate that overexpression of the combined EAAT2, GDH2, and NRF2 genes can provide neuroprotection after ischemic injury.

Original languageEnglish
Pages (from-to)180-187
Number of pages8
JournalJournal of Molecular Neuroscience
Volume66
Issue number2
DOIs
StatePublished - 1 Oct 2018

Keywords

  • EAAT2 GDH2
  • Gene therapy
  • Ischemic injury
  • Nrf2
  • Stroke

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