(Stroke. 1996;27:1688-1693.)
© 1996 American Heart Association, Inc.
Articles |
Gene Therapy for Cerebral Vascular Disease
the Departments of Internal Medicine and Pharmacology, University of Iowa College of Medicine (Iowa City).
Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, 200 Hawkins Dr, E315 GH, Iowa City, IA 52242-1081.
Background Gene transfer to peripheral arteries has been accomplished with catheter-based approaches. Recently, gene transfer to the carotid artery and intracranial vessels has been achieved both in vitro and in vivo. Although gene therapy for cerebral vascular disease may not be accomplished for years, currently available methods probably will allow novel approaches to the study of vascular biology.
Purpose This mini-review summarizes current methodology and describes some potential goals of gene therapy. Transfection of vessels might be used to prevent vasospasm after subarachnoid hemorrhage, stimulate growth of collateral blood vessels, stabilize atherosclerotic plaques, and prevent restenosis after angioplasty. Gene transfer approaches also may be useful in treating ischemia by inhibition or overexpression of cytokines and by effects on neurons. Some formidable barriers to gene therapy are the current lack of safe and effective vectors for gene transfer, the difficulty in delivering vectors to intracranial vessels, and the transience of transfection.
Conclusions At present, gene transfer is a promising tool for the study of vascular biology. Obstacles to gene therapy for cerebral vascular disease seem sufficiently large that new approaches, rather than refinement of current approaches, may be needed. Progress toward gene therapy probably will be made in steps rather than leaps.
Key Words: collateral circulation • gene targeting • genetic vectors • subarachnoid hemorrhage
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