Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease.
Neuronal progenitor cells (NPCs) may provide dopaminergic neurons for the treatment of Parkinson's disease (PD). However, transplantation of NPCs into the striatum by current methods has had limited success. It is possible to reverse the symptoms of PD in model rats but difficult to reverse them in humans because the number of dopaminergic neurons generated from NPCs is low. We transduced the von Hippel-Lindau (VHL) gene into NPCs isolated from embryonic rat brain. The NPCs with the transduced VHL gene efficiently differentiated into tyrosine hydroxylase-positive neurons in vitro. NPCs with the transduced VHL gene, which were labeled in advance with bromodeoxyuridine, were transplanted into the striatum of a rat model of PD. Numerous bromodeoxyuridine-tyrosine hydroxylase double-labeled cells were seen close to the transplant site, showing that the transplanted cells efficiently generated new dopaminergic neurons within the host striatum. Moreover, all of the animals with NPCs with VHL showed a remarkable decrease in apomorphine-induced rotations. These findings show that NPCs with the VHL gene can efficiently generate dopaminergic neurons and that a sufficient number of dopaminergic neurons can develop from them to reverse the symptoms of PD in humans. VHL gene transduction provides a new therapeutic approach for treatment of PD.
Yamada
Hitoshi
H
Yokohama Neurology Clinic and School of Medicine, Yokohama City University, 1-211-1 Mutsukawa, Minami-ku, Yokohama 232-0066, Japan. yokohama-neuro@mtd.biglobe-ne.jp
Dezawa
Mari
M
Shimazu
Seiichiro
S
Baba
Masaya
M
Sawada
Hajime
H
Kuroiwa
Yoshiyuki
Y
Yamamoto
Isao
I
Kanno
Hiroshi
H
D000818:Animals; D016380:Brain Tissue Transplantation; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D004298:Dopamine / Q000378:metabolism; D004622:Embryo, Mammalian; D016332:Fetal Tissue Transplantation; D006085:Graft Survival; D006801:Humans; D007150:Immunohistochemistry; D008025:Ligases / Q000235:genetics*; D008297:Male; D023421:Models, Animal; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology / Q000637:transplantation*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014161:Transduction, Genetic; D025521:Tumor Suppressor Proteins; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein
D025521:Tumor Suppressor Proteins; D016627:Oxidopamine; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D008025:Ligases; C497446:VHL protein, human; D004298:Dopamine