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Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease

Huntington's disease is a genetic disorder that results from degeneration of striatal neurons, particularly those containing GABA ( gamma -aminobutyric acid). There is no effective treatment for preventing or slowing this neuronal degeneration. Ciliary neurotrophic factor (CNTF) is a trophic factor... Full description

Journal Title: Nature 1997, Vol.386(6623), p.395
Main Author: Dwaine F. Emerich
Other Authors: Shelley R. Winn , Philippe M. Hantraye , Marc Peschanski , Er-Yun Chen , Yaping Chu , Patricia Mcdermott , E. Edward Baetge , Jeffrey H. Kordower
Format: Electronic Article Electronic Article
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ID: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/386395a0
Link: http://dx.doi.org/10.1038/386395a0
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recordid: nature_a10.1038/386395a0
title: Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease
format: Article
creator:
  • Dwaine F. Emerich
  • Shelley R. Winn
  • Philippe M. Hantraye
  • Marc Peschanski
  • Er-Yun Chen
  • Yaping Chu
  • Patricia Mcdermott
  • E. Edward Baetge
  • Jeffrey H. Kordower
subjects:
  • Cortex (Motor)
  • Neuropathy
  • Striatum
  • Animal Models
  • Neurodegeneration
  • Implants
  • Neuroprotective Agents
  • Huntington'S Chorea
  • General
  • Cellular Based
  • Featured Papers and Books
  • Miscellaneous, Reviews
  • Neurotropic Factors and Their Receptors
  • Motor Systems and Movement Disorders
  • Primates
  • Neuroprotective Agents
  • Cntf Protein
  • Ciliary Neurotrophic Factor
  • Encapsulated Cells
  • Featured Paper
  • Gamma -Aminobutyric Acid
  • Monkeys
  • Quinolinic Acid
ispartof: Nature, 1997, Vol.386(6623), p.395
description: Huntington's disease is a genetic disorder that results from degeneration of striatal neurons, particularly those containing GABA ( gamma -aminobutyric acid). There is no effective treatment for preventing or slowing this neuronal degeneration. Ciliary neurotrophic factor (CNTF) is a trophic factor for striatal neurons and therefore a potential therapeutic agent for Huntington's disease. Here we evaluate CNTF as a neuroprotective agent in a non-human primate model of Huntington's disease. We gave cynomolgus monkeys intrastriatal implants of polymer-encapsulated baby hamster kidney fibroblasts that had been genetically modified to secrete human CNTF. One week later, monkeys received unilateral injections of quinolinic acid into the previously implanted striatum to reproduce the neuropathology seen in Huntington's disease. Human CNTF was found to exert a neuroprotective effect on several populations of striatal cells, including GABAergic, cholinergic and diaphorase-positive neurons which were all destined to die following administration of quinolinic acid. Human CNTF also prevented the retrograde atrophy of layer V neurons in motor cortex and exerted a significant protective effect on the GABAergic innervation of the two important target fields of the striatal output neurons (the globus pallidus and pars reticulata of the substantia nigra). Our results show that human CNTF has a trophic influence on degenerating striatal neurons as well as on critical non-striatal regions such as the cerebral cortex, supporting the idea that human CNTF may help to prevent the degeneration of vulnerable striatal populations and cortical-striatal basal ganglia circuits in Huntington's disease.
language:
source:
identifier: ISSN: 0028-0836 ; E-ISSN: 1476-4687 ; DOI: 10.1038/386395a0
fulltext: fulltext
issn:
  • 0028-0836
  • 00280836
  • 1476-4687
  • 14764687
url: Link


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titleProtective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease
creatorDwaine F. Emerich ; Shelley R. Winn ; Philippe M. Hantraye ; Marc Peschanski ; Er-Yun Chen ; Yaping Chu ; Patricia Mcdermott ; E. Edward Baetge ; Jeffrey H. Kordower
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subjectCortex (Motor) ; Neuropathy ; Striatum ; Animal Models ; Neurodegeneration ; Implants ; Neuroprotective Agents ; Huntington'S Chorea ; General ; Cellular Based ; Featured Papers and Books ; Miscellaneous, Reviews ; Neurotropic Factors and Their Receptors ; Motor Systems and Movement Disorders ; Primates ; Neuroprotective Agents ; Cntf Protein ; Ciliary Neurotrophic Factor ; Encapsulated Cells ; Featured Paper ; Gamma -Aminobutyric Acid ; Monkeys ; Quinolinic Acid;
descriptionHuntington's disease is a genetic disorder that results from degeneration of striatal neurons, particularly those containing GABA ( gamma -aminobutyric acid). There is no effective treatment for preventing or slowing this neuronal degeneration. Ciliary neurotrophic factor (CNTF) is a trophic factor for striatal neurons and therefore a potential therapeutic agent for Huntington's disease. Here we evaluate CNTF as a neuroprotective agent in a non-human primate model of Huntington's disease. We gave cynomolgus monkeys intrastriatal implants of polymer-encapsulated baby hamster kidney fibroblasts that had been genetically modified to secrete human CNTF. One week later, monkeys received unilateral injections of quinolinic acid into the previously implanted striatum to reproduce the neuropathology seen in Huntington's disease. Human CNTF was found to exert a neuroprotective effect on several populations of striatal cells, including GABAergic, cholinergic and diaphorase-positive neurons which were all destined to die following administration of quinolinic acid. Human CNTF also prevented the retrograde atrophy of layer V neurons in motor cortex and exerted a significant protective effect on the GABAergic innervation of the two important target fields of the striatal output neurons (the globus pallidus and pars reticulata of the substantia nigra). Our results show that human CNTF has a trophic influence on degenerating striatal neurons as well as on critical non-striatal regions such as the cerebral cortex, supporting the idea that human CNTF may help to prevent the degeneration of vulnerable striatal populations and cortical-striatal basal ganglia circuits in Huntington's disease.
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titleProtective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease
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