Transfer of the von Hippel-Lindau gene to neuronal progenitor cells in treatment for Parkinson's disease

Hitoshi Yamada, Mari Dezawa, Seiichiro Shimazu, Masaya Baba, Hajime Sawada, Yoshiyuki Kuroiwa, Isao Yamamoto, Hiroshi Kanno

研究成果: Article査読

33 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)352-359
ページ数8
ジャーナルAnnals of Neurology
54
3
DOI
出版ステータスPublished - 2003 9 1
外部発表はい

ASJC Scopus subject areas

  • 神経学
  • 臨床神経学

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