title: The delivery of tyrosine hydroxylase accelerates the neurorestoration of Macaca Rhesus model of Parkinson's disease provided by Neurturin.
abstract: Neurturin (NTN) is a desired candidate therapeutic gene for PD treatment, however, only neuroprotective effect may not work for PD clinical remission due to nearly 50% of the dopaminergic neurons have died way when symptoms appear. In this study, we constructed a bicistronic adenovirus expressing both Neurturin and tyrosine hydroxylase (TH). We hypothesized that the expression of NTN could provide neuroprotection to dopaminergic neurons and stop progressive neurodegeneration, while TH enhanced the synthesis of dopamine and accelerated the recovery of Parkinsonism. The chimeric adenovirus have been prepared and assayed in vitro and delivered into the target nucleuses of PD Macaca Rhesus models by MRI based stereotaxic injection. The observation assessments and physiological results indicated that compared to the group treated with NTN only, instant behavior recovery was seen after bicistronic adenovirus infusion. Although both groups displayed neuroprotection of dopaminergic neurons finally, the addition of TH genuinely accelerated animal behavior recovery, which showed great potential for clinical application.
authors: Institute of Medical Biology, Peking Union Medical College, Chinese Academy of Medical Science, Kunming 650118, People's Republic of China.
authors: Wenju
authors: W
authors: Wang
authors: Maosheng
authors: M
authors: Sun
authors: Hongjun
authors: H
authors: Li
authors: Wanpu
authors: W
authors: Wang
authors: Min
authors: M
authors: Yan
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004298:Dopamine / Q000096:biosynthesis; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000473:pathology; D005727:Ganglia, Spinal / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors; D008253:Macaca mulatta; D051101:Neurturin / Q000235:genetics* / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D013239:Stereotyped Behavior; D014709:Vero Cells
chemical_list: D051101:Neurturin; D011505:Protein-Tyrosine Kinases; D004298:Dopamine