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A direct gene transfer strategy via brain internal capsule reverses the biochemical defect in Tay-Sachs disease.

Authors
  • Martino, S
  • Marconi, P
  • Tancini, B
  • Dolcetta, D
  • De Angelis, M G Cusella
  • Montanucci, P
  • Bregola, G
  • Sandhoff, K
  • Bordignon, C
  • Emiliani, C
  • Manservigi, R
  • Orlacchio, A
Type
Published Article
Journal
Human Molecular Genetics
Publisher
Oxford University Press (OUP)
Publication Date
Aug 01, 2005
Volume
14
Issue
15
Pages
2113–2123
Identifiers
PMID: 15961412
Source
Medline
License
Unknown

Abstract

Therapy for neurodegenerative lysosomal Tay-Sachs (TS) disease requires active hexosaminidase (Hex) A production in the central nervous system and an efficient therapeutic approach that can act faster than human disease progression. We combined the efficacy of a non-replicating Herpes simplex vector encoding for the Hex A alpha-subunit (HSV-T0alphaHex) and the anatomic structure of the brain internal capsule to distribute the missing enzyme optimally. With this gene transfer strategy, for the first time, we re-established the Hex A activity and totally removed the GM2 ganglioside storage in both injected and controlateral hemispheres, in the cerebellum and spinal cord of TS animal model in the span of one month's treatment. In our studies, no adverse effects were observed due to the viral vector, injection site or gene expression and on the basis of these results, we feel confident that the same approach could be applied to similar diseases involving an enzyme defect.

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