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Intraputamenal Infusion of Exogenous Neurturin Protein Restores Motor and Dopaminergic Function in the Globus Pallidus of MPTP-Lesioned Rhesus Monkeys

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The neurorestorative effects of exogenous neurturin (NTN) delivered directly into the putamen via multiport catheters were studied in 10 MPTP-lesioned rhesus monkeys expressing stable parkinsonism. The parkinsonian animals were blindly assigned to receive coded solutions containing either vehicle (n = 5) or NTN (n = 5, 30 g/day). Both solutions were coinfused with heparin using convection-enhanced delivery for 3 months. The NTN recipients showed a significant and sustained behavioral improvement in their parkinsonian features during the treatment period, an effect not seen in the vehicle-treated animals. At study termination, locomotor activity levels were increased by 50% in the NTN versus vehicle recipients. Also, DOPAC levels were significantly increased by 150% ipsilateral (right) to NTN infusion in the globus pallidus, while HVA levels were elevated bilaterally in the NTN-treated animals by 10% on the left and 67% on the right hemisphere. No significant changes in DA function were seen in the putamen. Volumetric analysis of putamenal NTN labeling showed between-subject variation, with tissue distribution ranging from 214 to 744 mm3, approximately equivalent to 27–93% of area coverage. Our results support the concept that intraparenchymal delivery of NTN protein may be effective for the treatment of PD. More studies are needed to determine strategies that would enhance tissue distribution of exogenous NTN protein, which could contribute to optimize its trophic effects in the parkinsonian brain.

Keywords: MPTP; Neuroregeneration; Neurturin; Parkinson's disease; Putamen

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/096368908784423256

Affiliations: 1: Department of Anatomy & Neurobiology, University of Kentucky Medical Center, Lexington, KY, USA, Morris K. Udall Parkinson's Disease Research Center of Excellence, University of Kentucky Medical Center, Lexington, KY, USA 2: Department of Anatomy & Neurobiology, University of Kentucky Medical Center, Lexington, KY, USA, Department of Neurosurgery, Shandong Provincial Hospital, Shandong University, Jinan, Shandong, PR China 3: Department of Anatomy & Neurobiology, University of Kentucky Medical Center, Lexington, KY, USA

Publication date: April 1, 2008

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.
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