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  4. Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF
 
research article

Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF

Aebischer, P.  
•
Pochon, N. A.
•
Heyd, B.
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1996
Human Gene Therapy

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and contains a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.

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Type
research article
DOI
10.1089/hum.1996.7.7-851
Author(s)
Aebischer, P.  
Pochon, N. A.
Heyd, B.
Deglon, N.  
Joseph, J. M.
Zurn, A. D.
Baetge, E. E.
Hammang, J. P.
Goddard, M.
Lysaght, M.
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Date Issued

1996

Published in
Human Gene Therapy
Volume

7

Issue

7

Start page

851

End page

860

Subjects

Amyotrophic Lateral Sclerosis/ therapy

•

Animals

•

Capsules/chemistry/therapeutic use

•

Cell Line

•

Cell Transplantation/methods

•

Cells

•

Cultured

•

Ciliary Neurotrophic Factor

•

Clinical Protocols

•

Cricetinae

•

Ganciclovir/pharmacology

•

Gene Therapy/ methods

•

Genetic Vectors/genetics/pharmacology/toxicity

•

Humans

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Kidney/cytology

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Nerve Tissue Proteins/adverse effects/ genetics/ therapeutic use

•

Polymers/chemistry/therapeutic use

•

Primates

•

Prostheses and Implants

•

Rats

•

Sheep

•

Simplexvirus/enzymology/genetics

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Thymidine Kinase/genetics

•

Transfection

Note

Division of Surgical Research & Gene Therapy Center, Lausanne University Medical School, Switzerland.

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LEN  
Available on Infoscience
March 9, 2007
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/3678
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