Combined Gene Therapy to Reduce the Neuronal Damage in the Mouse Model of Focal Ischemic Injury
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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.
KeywordsStroke Ischemic injury Gene therapy EAAT2 GDH2 Nrf2
This study received funds as a scholarship from Mr. Martin Davis to LM.
Compliance with Ethical Standards
DO holds several patents related to gene therapy in neurodegenerative diseases. All were assigned to “Ramot at Tel Aviv University.” DO is a consultant to “Brainstorm Cell Therapeutics.” The other authors have nothing to disclose.
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