Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington's disease

Mittoux, V., Joseph, J. M., Conde, F., Palfi, S., Dautry, C., Poyot, T., Bloch, J., Deglon, N., Ouary, S., Nimchinsky, E. A., Brouillet, E., Hof, P. R., Peschanski, M., Aebischer, P., Hantraye, P. (May 2000) Restoration of cognitive and motor functions by ciliary neurotrophic factor in a primate model of Huntington's disease. Human Gene Therapy, 11 (8). pp. 1177-1187. ISSN 1043-0342

URL: http://www.ncbi.nlm.nih.gov/pubmed/10834619
DOI: 10.1089/10430340050015220

Abstract

Huntington's disease (HD) is an inherited disorder characterized by cognitive impairments, motor deficits, and progressive dementia, These symptoms result from progressive neurodegenerative changes mainly affecting the neostriatum, This pathology is fatal in 10 to 20 years and there is currently no treatment for HD, Early in the course of the disease, initial clinical manifestations are due to striatal neuronal dysfunction, which is later followed by massive neuronal death. A major therapeutic objective is therefore to reverse striatal dysfunction prior to cell death. Using a primate model reproducing the clinical features and the progressive neuronal degeneration typical of HD, we tested the therapeutic effects of direct intrastriatal infusion of ciliary neurotrophic factor (CNTF). To achieve a continuous delivery of CNTF over the full period of evaluation, we took advantage of the macroencapsulation technique. Baby hamster kidney (BHK) cells previously engineered to produce human CNTF mere encapsulated into semipermeable membranes and implanted bilaterally into striata. We show here that intracerebral delivery of low doses of CNTF at the onset of symptoms not only protects neurons from degeneration but also restores neostriatal functions. CNTF-treated primates recovered, in particular, cognitive and motor functions dependent on the anatomofunctional integrity of frontostriatal pathways that mere distinctively altered in this HD model. These results support the hypothesis that CNTF infusion into the striatum of HD patients not only could block the degeneration of neurons but also alleviated motor and cognitive symptoms associated with persistent neuronal dysfunction.

Item Type: Paper
Uncontrolled Keywords: AMYOTROPHIC-LATERAL-SCLEROSIS ORPHANIN-FQ SUCCINATE-DEHYDROGENASE STRIATAL DEGENERATION 3-NITROPROPIONIC ACID NEURODEGENERATIVE DISEASES NEUROPOIETIC CYTOKINES FACTOR RHCNTF NEURONS PROTEIN
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > ciliary neurotrophic factor
diseases & disorders > cancer > cancer types > huntington's disease
organism description > animal > mammal > primates
CSHL Authors:
Communities: CSHL labs > Svoboda lab
Depositing User: Matt Covey
Date: May 2000
Date Deposited: 28 Jan 2014 20:55
Last Modified: 28 Jan 2014 20:55
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29442

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