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Kis, A. and Wild, C. and Bodamer, O. (2008): Enzyme Replacement Therapy for Lysosomal Storage Diseases. Decision Support Document 19.

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Abstract

Lysosomal storage diseases (LSD) are a heterogenous group of more than 40 inborn errors of metabolism that are due to specific defects of lysosomal en-zymes, lysosomal membrane proteins or transporters respectively. All LSD are inherited autosomal recessively with the exception of MPS II (M. Hunter), Fabry Disease and Danon Disease that are inherited as X chromosomal traits. Although individually rare their cumulative prevalence may be as high as 1:800 in certain ethnic populations.

LSD in general are progressive multiorgan disorder with about 50% having significant central nervous involvement. Each LSD comprises a more or less unique clinical spectrum with patients at the more severe end showing in-creased morbidity and mortality whereas patients at the milder end of the spectrum having only subtle clinical signs. Patients with mild disease may of-ten go unrecognized for many years.

Therapy of LSD consisted mainly of palliative treatment until the recent de-velopment of enzyme replacement therapies for Gaucher, Pompe and Fabry Diseases as well as Mucopolysaccharidosis types I and II (MPS I/II)

Lysosomes are intracellular organelles that encompass numerous hy-drolases and other enzymes that break down different compounds derived from intermediary metabolism such as complex lipids, carbohydrates and others.

During the last years the interest for the LSD has significantly increased due to the development of novel therapies including enzyme replacement thera-pies (ERT) and substrate inhibition therapy. Additional therapies such as chaperone therapy are currently evaluated in phase I and II trials. Currently ERT are available for MPS I, II, VI, Fabry, Pompe and Gaucher diseases. In ad-dition SRT has been licensed for Gaucher disease.

The aim of this paper is to give a brief overview of the treatable LSD, to summarise the guidelines for diagnosis, treatment and disease management, to summarise data from ERT registers and to analyse eventual fields of con-flict. For this purpose a thorough Medline search up to August 2008 was per-formed using the following key words: MPS I, MPS II, MPS VI, Pompe, Fabry, Gaucher, enzyme replacement therapy, treatment and registry respectively. In addition all pharmaceutical companies involved in manufacturing recom-binant enzyme and/or substrate inhibition therapies were contacted for fur-ther information. These companies included Actelion, Biomarin, Genzyme and Shire.

Item Type:Decision Support Document
Keywords:Enzyme Replacement Therapy, ERT, Lysosomal Storage Disease, LSD, Mucopolysaccaridosis, MPS, Pompe Disease, Fabry Disease, Gaucher Disease
Subjects:QU Biochemistry > QU 135-144 Enzymes
QZ Pathology > QZ 50 Medical genetics
WL Nervous system > WL 200-405 Central nervous system. Disorders. Therapeutics
Language:English
Series Name:Decision Support Document
Number:19
Deposited on:05 Nov 2008 17:39
Last Modified:05 Nov 2008 17:39

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