Current Gene Therapy

Ignacio Anegon
Director INSERM UMR 1064-Center for Research in Transplantation and Immunology
CHU de Nantes. 30, boulevard
Nantes
France

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Therapies for Neurological Disease in the Mucopolysaccharidoses

Author(s): Donald S. Anson, Chantelle McIntyre, Sharon Byers.

Abstract:

Intravenous enzyme replacement therapy has been developed as a viable treatment for most of the somatic pathologies associated with the mucopolysaccharide storage disorders. However, approximately two thirds of individuals affected by a mucopolysaccharide storage disorder also display neurological disease, in these instances intravenous enzyme replacement therapy is not viable as the blood-brain barrier severely limits enzyme distribution from the peripheral circulation into the central nervous system. Accordingly, much research is now focussed on developing therapies that specifically address neurological disease, or somatic and neurological disease in combination. Therapies designed to address the underlying cause of central nervous system pathology, that is the lysosomal storage itself, can be broadly divided into two groups, those that continue the rationale of enzyme replacement, and those that address the supply side of the storage equation; that is the production of storage material. Enzyme replacement can be further divided by technology (principally direct enzyme replacement, gene replacement and cell transplantation). Here we review the current state of the art for these strategies and suggest possible future directions for research in this field. In particular, we suggest that any one approach in itself is unlikely to be as efficacious as a carefully considered combination therapy, be it a combination of some sort of enzyme replacement with substrate deprivation, or a combination of two different replacement technologies or strategies.

Keywords: Disease, glycosaminoglycan, mucopolysaccharidosis, neurological, storage, therapy, Enzyme replacement, CNS pathology, BLOOD-BRAIN BARRIER, AAV vector, ependyma

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Article Details

VOLUME: 11
ISSUE: 2
Year: 2011
Page: [132 - 143]
Pages: 12
DOI: 10.2174/156652311794940791
Price: $58