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| Protective effect of encapsulated cells producing neurotrophic factor CNTF in a monkey model of Huntington's disease |
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| Author(s): Emerich DF, Winn SR, Hantraye PM, Peschanski M, Chen EY, Chu YP, McDermott P, Baetge EE, Kordower JH |
| Source: NATURE Volume: 386 Issue: 6623 Pages: 395-399 Published: MAR 27 1997 |
| Times Cited: 174 References: 29 |
| Abstract: Huntington's disease is a genetic disorder that results from degeneration of striatal neurons, particularly those containing GABA (gamma-aminobutyric acid)(1). There is no effective treatment for preventing or slowing this neuronal degeneration. Ciliary neurotrophic factor (CNTF) is a trophic factor for striatal neurons(2,3) and therefore a potential therapeutic agent for Huntington's disease. Here we evaluate CNTF as a neuroprotective agent in a nonhuman 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(4,5). 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. |
| Document Type: Article |
| Language: English |
Addresses:
1. CYTOTHERAPEUT INC, PROVIDENCE, RI 02906 USA
2. OREGON HLTH SCI UNIV, DEPT SURG, PORTLAND, OR 97201 USA
3. SVC HOSP FREDER JOLIET, CNRS, URA 1285, F-91406 ORSAY, FRANCE
4. INSERM, U421, FAC MED, F-94010 CRETEIL, FRANCE
5. RUSH PRESBYTERIAN ST LUKES MED CTR, RES CTR BRAIN REPAIR, CHICAGO, IL 60612 USA
6. RUSH PRESBYTERIAN ST LUKES MED CTR, DEPT NEUROL SCI, CHICAGO, IL 60612 USA |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: WQ170 |
| ISSN: 0028-0836 |
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