Prospects for the treatment of stroke using gene therapy.
Recent advances have demonstrated the use of gene therapy in the treatment of stroke in experimental animal models of focal ischemia, global ischemia and subarachnoid hemorrhage. Several different vectors for gene transfer have been studied including herpes simplex virus, adenovirus, adeno-associated virus and liposomes. Genetically modified cell lines (e.g., bone marrow-derived cells) have been studied for ex vivo gene therapy. The effects of gene transfer to several brain regions including the striatum, cortex, hippocampus, subarachnoid space and blood vessels are reviewed. Targets of gene therapy, such as molecular cascades after ischemia onset (Ca2+ influx, ATP loss, increased nitric oxide) and events associated with apoptosis are also reviewed, in addition to how gene transfer may be used to understand pathomechanisms underlying ischemic injury and the temporal therapeutic windows following ischemia within which protective effects of gene therapy have been achieved. The prospects for gene therapy for stroke are discussed in light of these findings and it is concluded that solutions to key technological problems will allow gene therapy to be a viable treatment modality.
Zhao
Heng
H
Department of Neurosurgery, Stanford University, Stanford, 300 Pasteur Drive R200, Stanford, CA 94305, USA.
Yenari
Midori A
MA
Sapolsky
Robert M
RM
Steinberg
Gary K
GK