Gene therapy of cerebrovascular disease

K K Jain MD (Dr. Jain is a consultant in neurology and has no relevant financial relationships to disclose.)
Originally released December 23, 1999; last updated August 30, 2020; expires August 30, 2023


The aim of gene therapy in stroke is to prevent secondary damage after cerebral infarction. Treatments are also aimed at correcting the pathology in blood vessels supplying the brain. This article describes various experimental techniques for gene transfer in cerebrovascular disorders. Direct gene transfer to the brain in acute infarction is unlikely to be practical, but implantation of genetically modified cells releasing neurotrophic factors may aid in recovery in the chronic poststroke stage. Gene therapy also has promising applications in diseases of blood vessels supplying the brain.

Key points


• The aim of gene therapy in stroke is to prevent secondary damage after an episode of cerebral ischemia or infarction.


• Gene therapy is also being investigated for disorders of cerebral blood vessels.


• Experiments in animal models have demonstrated the safety and efficacy of gene therapy for cerebrovascular diseases.


• Clinical trials for applications in cerebrovascular diseases in humans are anticipated in the future.

Historical note and terminology

Gene therapy can be broadly defined as “the transfer of defined genetic material to specific target cells of a patient for the ultimate purpose of preventing or altering a particular disease state.” Carriers or delivery vehicles for therapeutic genetic material, called “vectors,” are usually viral, but several nonviral techniques are being used as well. Ex vivo gene therapy involves the genetic alterations of cells (cell lines or human cells), mostly by use of viral vectors, prior to implanting these into the tissues of the living body. In vivo gene therapy means direct introduction of genetic material into the human body. It can be accomplished by use of nonviral vectors. In vivo gene delivery may be local (in situ) or systemic. In situ gene therapy means the introduction of genetic material directly into a localized area in the human body. Gene therapy does not merely imply gene transfer but covers other methods of treating diseases at the genetic level. Genes and DNA are now being introduced without the use of vectors, and various techniques are being used to modify the function of genes in vivo without gene transfer, such as gene repair and gene editing. Antisense therapeutics are used to block production of abnormal disease-related proteins. This can be achieved by antisense oligonucleotides, synthetic short segments of DNA or RNA that can hybridize to sequences in the RNA target. An alternative antisense approach is the use of ribozymes that catalyze RNA cleavage, also called ribozyme gene therapy. By cleaving a target RNA, ribozymes inhibit the translation of RNA into protein, thus, stopping the expression of a specific gene. The term "genetic engineering" applies to genetic manipulation of living cells such as stem cells and implantation of genetically engineered cells into the living body to produce therapeutic proteins; this can be considered a form of gene therapy. Neurosurgeons refer to gene therapy as "cellular and molecular" neurosurgery.

Historical landmarks in the development of gene therapy are described in the introductory article. The development of gene therapy for many neurologic indications has progressed rapidly during the past decade and has been reviewed in other articles on this topic.

Gene transfer into the blood vessels was reported in 1989 when pig endothelial cells, transfected with a retrovirus expressing beta-galactosidase, were injected intraluminally into pig iliofemoral arteries (Nabel et al 1989). Considerable animal experimental work has been done on vascular gene therapy. Neurologists interested in stroke care, as well as those interested in cerebrovascular neurosurgery, should be familiar with the developments in gene therapy. It is anticipated that gene therapy will be introduced for clinical use in the treatment of certain cerebrovascular disease indications within the next decade.

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