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New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy

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Abstract

During the last few years, much progress has been made in the treatment of lysosomal storage disorders. In the past, no specific therapy was available for the affected patients, and management consisted solely of supportive care and treatment of complications. Since enzyme replacement therapy has been successfully introduced for patients with Gaucher disease, this principle of treatment has been taken into consideration for other lysosomal storage disorders as well. Clinical trials could demonstrate the clinical benefit of this therapeutic principle in Fabry disease, mucopolysaccharidoses type I, II and VI and in Pompe disease. However, the usefulness of enzyme replacement therapy is limited due to the fact that a given enzyme preparation does not have beneficial effects on all aspects of a disorder in the same degree. Additionally, clinical studies have shown that many symptoms of a lysosomal storage disorder even after long-term treatment are no more reversible. A further novel therapeutic option for lysosomal storage disorders consists of the application of small molecules that either inhibit a key enzyme which is responsible for substrate synthesis (substrate deprivation) or act as a chaperone to increase the residual activity of the lysosomal enzyme (enzyme enhancing therapy). Various gene therapeutic techniques (in vivo and ex vivo technique) have been developed in order to administer the gene that is defective in a patient to the bloodstream or directly to the brain in order to overcome the blood–brain barrier. This review will give an insight into these newly developed therapeutic strategies and will discuss their advantages and limitations.

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Acknowledgments

Declaration of conflict of interest: the author has received unrestricted scientific grants from Shire Human Genetic Therapies, Genzyme Corp., Actelion Pharmaceuticals Ltd. and Biomarin Pharmaceutical Inc.

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    Michael Beck

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Beck, M. New therapeutic options for lysosomal storage disorders: enzyme replacement, small molecules and gene therapy. Hum Genet 121, 1–22 (2007). https://doi.org/10.1007/s00439-006-0280-4

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