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Therapeutic approaches for neuronopathic lysosomal storage disorders
Author(s) -
Schiffmann Raphael
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9047-0
Subject(s) - substrate reduction therapy , enzyme replacement therapy , lysosomal storage disease , medicine , genetic enhancement , disease , central nervous system , hematopoietic stem cell transplantation , stem cell , transplantation , cell therapy , bioinformatics , neuroscience , biology , gene , microbiology and biotechnology , biochemistry
Therapy of the central nervous system (CNS) manifestations of lysosomal storage diseases (LSDs) has remained a major challenge because of its inability to deliver therapeutic agents efficiently across the intact blood–brain barrier. Non‐specific therapies such as hematopoietic stem cell transplantation have been useful in globoid cell leukodystrophy (Krabbe disease) and in some mucopolysaccharidoses. Anti‐inflammatory agents also show promise as adjuvant therapy. High doses of replacement therapy with native or modified enzyme show renewed promise for correction of CNS cells. Alternatively, small molecules can enter the brain relatively easily and promote reduction of accumulated substrate or function as pharmacological chaperones to enhance the level of the deficient enzyme. Gene therapy is still being developed and tested in patients. It is therefore likely that, thanks to a better understanding of disease mechanism, a variety of therapeutic approaches, used alone or in combination, will be useful to treat the devastating neurological complications of LSDs.