Significant behavioral recovery in Parkinson's disease model by direct intracerebral gene transfer using continuous injection of a plasmid DNA-liposome complex.
As an alternative to virus-mediated gene transfer, we previously demonstrated a simple, safe, and efficient transfer of foreign gene into the central nervous system using continuous injection of a plasmid DNA-cationic liposome complex. To explore whether this approach can be applied to the treatment of certain neurological disorders, we used an experimental model of Parkinson's disease (PD) in the present study. Following continuous injection for 7 days, tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC) genes carried by a bovine papilloma virus-based plasmid vector were efficiently introduced into glial cells in the striatum of 6-hydroxydopamine-lesioned rats. Significant recovery in apomorphine-induced rotational behavior of PD models was obtained by transfection of TH gene and this effect continued for up to 5 weeks after injection. Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone. We suggest that this approach is a controllable and manageable alternative to other methods of gene therapy for the treatment of PD.
Imaoka
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Department of Neurological Surgery, Okayama University Medical School, Japan.
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Ohmoto
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Nagatsu
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D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000235:genetics*; D052688:Bovine papillomavirus 1 / Q000235:genetics*; D002417:Cattle; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D005998:Glycine / Q000031:analogs & derivatives*; D007267:Injections; D008081:Liposomes; D009043:Motor Activity; D016627:Oxidopamine / Q000494:pharmacology; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000628:therapy*; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D013096:Spermine / Q000031:analogs & derivatives*; D013565:Sympatholytics / Q000494:pharmacology; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics*
D004337:Drug Carriers; D008081:Liposomes; D013565:Sympatholytics; C061134:dioctadecylamidoglycylspermine; D013096:Spermine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D001142:Aromatic-L-Amino-Acid Decarboxylases; D005998:Glycine