Triple-Gene Therapy for Stroke: A Proof-of-Concept in Vivo Study in Rats

Frontiers in Pharmacology
Mikhail E SokolovRustem R Islamov

Abstract

Natural brain repair after stroke is extremely limited, and current therapeutic options are even more scarce with no clinical break-through in sight. Despite restricted regeneration in the central nervous system, we have previously proved that human umbilical cord blood mono-nuclear cells (UCB-MC) transduced with adenoviral vectors carrying genes encoding vascular endothelial growth factor (VEGF), glial cell-derived neurotrophic factor (GDNF), and neural cell adhesion molecule (NCAM) successfully rescued neurons in amyotrophic lateral sclerosis and spinal cord injury. This proof-of-principle project was aimed at evaluating the beneficial effects of the same triple-gene approach in stroke. Rats subjected to distal occlusion of the middle cerebral artery were treated intrathecally with a combination of these genes either directly or using our cell-based (UCB-MC) approach. Various techniques and markers were employed to evaluate brain injury and subsequent recovery after treatment. Brain repair was most prominent when therapeutic genes were delivered via adenoviral vector- or UCB-MC-mediated approach. Remodeling of brain cortex in the stroke area was confirmed by reduction of infarct volume and attenuated neural cell death, deplet...Continue Reading

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Citations

Jul 9, 2020·Medicinal Research Reviews·Maria Zakharova
Sep 21, 2018·Frontiers in Neurology·Olivera RajkovicEmmanuel Pinteaux
Sep 24, 2020·International Journal of Molecular Sciences·Vage MarkosyanRustem Islamov
Jan 7, 2021·Expert Opinion on Drug Delivery·Andrea PerrelliSaverio Francesco Retta
Oct 15, 2020·International Journal of Molecular Sciences·Dejan NikolicIvana Novakovic
Mar 28, 2020·Current Molecular Medicine·Maryam ShahiAli Abedelahi

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Methods Mentioned

BETA
transgenic
Fluorescence

Software Mentioned

Zen
ImageJ
R
Evrogen

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