Gene therapy for ischemic brain diseases.
We discuss possible gene therapies for the treatment of ischemic diseases in the central nervous system (CNS). These therapies aim at the prevention of carotid artery restenosis, stimulation of angiogenesis for ischemic brain, protection of neurons against ischemia, and prevention of vasospasm due to subarachnoid hemorrhage (SAH). Carotid artery restenosis can perhaps be approached by preventing vascular smooth muscle cell proliferation via gene therapy in addition to surgical treatment. Cerebral angiogenesis therapy might be applicable to moyamoya disease. Gene therapies with VEGF and HGF to stimulate angiogenesis have been successful in muscle; however, efficacy in the CNS is unknown. Gene transfection efficiency of viral vectors has been poor in the CNS, and the safety of such vectors is questionable. Therefore, development of gene therapy is for neural protection and prevention of vasospasm due to SAH has been limited. Infusion of HVJ-AVE liposomes into monkey cerebrospinal fluid (CSF) space yielded wide-spread gene transfection. HVJ-AVE liposomes may be a promising vector for use in the human CNS. Few currently available gene therapies appear to be options for clinical treatment of cerebral ischemia despite many experimental designs. In addition to the inherent difficulties of treating the CNS, vectors and methods for introducing vectors into the CNS must be improved.
Saitoh
Youichi
Y
Department of Neurosurgery, Division of Gene Therapy Science, Osaka University School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. neurosaitoh@mbk.nifty.com
Kato
Amami
A
Hagihara
Yasushi
Y
Kaneda
Yasufumi
Y
Yoshimine
Toshiki
T
D000818:Animals; D002545:Brain Ischemia / Q000517:prevention & control / Q000628:therapy*; D016893:Carotid Stenosis / Q000517:prevention & control; D015316:Genetic Therapy; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009474:Neurons / Q000378:metabolism; D051381:Rats; D013345:Subarachnoid Hemorrhage / Q000150:complications; D020301:Vasospasm, Intracranial / Q000517:prevention & control