Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF.

Détails

ID Serval
serval:BIB_3FBE992F810D
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Neuroprotective gene therapy for Huntington's disease using a polymer encapsulated BHK cell line engineered to secrete human CNTF.
Périodique
Human Gene Therapy
Auteur(s)
Bachoud-Lévi A.C., Déglon N., Nguyen J.P., Bloch J., Bourdet C., Winkel L., Rémy P., Goddard M., Lefaucheur J.P., Brugières P., Baudic S., Cesaro P., Peschanski M., Aebischer P.
ISSN
1043-0342 (Print)
ISSN-L
1043-0342
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
11
Numéro
12
Pages
1723-1729
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Huntington's disease (HD) is an autosomal dominant genetic disease with devastating clinical effects on cognitive, psychological, and motor functions. These clinical symptoms primarily relate to the progressive loss of medium-spiny GABA-ergic neurons of the striatum. There is no known treatment to date. Several neurotrophic factors have, however, demonstrated the capacity to protect striatal neurons in various experimental models of HD. This includes the ciliary neurotrophic factor (CNTF), the substance examined in this protocol. An ex vivo gene therapy approach based on encapsulated genetically modified BHK cells will be used for the continuous and long-term intracerebral delivery of CNTF. A device, containing up to 106 human CNTF-producing BHK cells surrounded by a semipermeable membrane, will be implanted into the right lateral ventricle of 6 patients. Capsules releasing 0.15-0.5 microg CNTF/day will be used. In this phase I study, the principal goal will be the evaluation of the safety and tolerability of the procedure. As a secondary goal, HD symptoms will be analyzed using a large battery of neuropsychological, motor, neurological, and neurophysiological tests and the striatal pathology monitored using MRI and PET-scan imaging. It is expected that the gene therapy approach described in this protocol will mitigate the side effects associated with the peripheral administration of recombinant hCNTF and allow a well-tolerated, continuous intracerebroventricular delivery of the neuroprotective factor.
Mots-clé
Animals, Cell Line, Cerebral Ventricles/metabolism, Ciliary Neurotrophic Factor/genetics, Ciliary Neurotrophic Factor/metabolism, Clinical Protocols, Clinical Trials, Phase I as Topic, Cricetinae, Gene Transfer Techniques, Genetic Therapy, Humans, Huntington Disease/therapy, Patient Selection
Pubmed
Web of science
Création de la notice
06/02/2008 11:03
Dernière modification de la notice
20/08/2019 14:37
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