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(Circulation Research. 2000;87:719.)
© 2000 American Heart Association, Inc.

Editorials

Adventure of Gene Therapy Into the Brain: A New Era for Cardiovascular Gene Therapy

Ryuichi Morishita

From the Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Suita, Japan.

Correspondence to Ryuichi Morishita, MD, PhD, Associate Professor, Division of Gene Therapy, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565, Japan. E-mail morishit@geriat.med.osaka-u.ac.jp\ © 2000 American Heart Association, Inc.

Key Words: central nervous system • stroke • gene therapy • blood-brain barrier • subarachnoid hemorrhage

	Introduction

 
Gene therapy is emerging as a potential strategy for the treatment of cardiovascular diseases such as peripheral arterial disease, myocardial infarction, restenosis after angioplasty, and vascular bypass graft occlusion, for which current therapy is often inadequate. The first federally approved human gene therapy protocol started on September 14, 1990, in patients with adenosine deaminase deficiency. Ten years after the commencement of the first trial, more than 30 clinical studies of gene therapy for cardiovascular disease are under investigation. First, Isner and colleagues demonstrated the potential utility of gene therapy using an angiogenic growth factor (vascular endothelial growth factor [VEGF]) for the treatment of critical limb ischemia in human patients.^{1 2} More recently, his group revealed the usefulness of gene therapy using VEGF to treat ischemic heart disease.^{3 4} Although there are still many unresolved issues, human gene therapy for cardiovascular disease is now becoming a reality.

	Novel Therapeutic Strategy to Treat Vasospasm After Subarachnoid Hemorrhage (SAH)

 
In addition to the diseases cited above, the study of Toyoda et al⁵ in this issue of Circulation Research identifies vasospasm after SAH as another potential target for gene therapy. These investigators transfected the gene of calcitonin gene–related peptide (CGRP), a potent vasodilator, into the cisterna magna of rabbits using adenovirus. Interestingly, transfection of CGRP gene ameliorated cerebral vasoconstriction after experimental SAH. Although delayed, prolonged arterial constriction after SAH can lead to brain ischemia and infarction, there is no known effective pharmacotherapy. Vasospasm occurs in 30% to 40% of patients after SAH and is the leading cause of mortality and morbidity in SAH. Previous reports demonstrated . . . [Full Text of this Article]