Significance of immune response to enzyme-replacement therapy for patients with a lysosomal storage disorder

Mucopolysaccharidosis type VI (MPS VI), or Maroteaux-Lamy syndrome, is a lysosomal storage disorder that results from a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase or arylsulfatase B (ASB). It is a relatively rare disorder, with an estimated incidence of 1 in 248,000 to 1 in 300,000. The diagnosis is made on the basis of findings of elevated urine glycosaminoglycans and a deficiency of ASB activity in leukocytes or cultured fibroblasts. In treatment of MPS VI, enzyme replacement therapy (galsulfase; human recombinant ASB enzyme) became available. Infusions of galsulfase were generally well tolerated. But in some patients, infusion-associated reactions including rash, urticaria, headache, hypotension, nausea, and vomiting were documented and were managed successfully by interrupting or slowing the rate of infusion and/or by the administration of antihistamines, antipyretics, corticosteroids, or oxygen. Here, we report a case with MPS VI who developed thrombocytopenia after third dose of therapy. To the best of our knowledge, this is the first report about thrombocytopenia associated with galsulfase therapy in the literature. Additionally, with this report, we want to share our approach for this case.

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Proteomics to identify signature proteins in patients likely to mount an immune response to enzyme replacement therapy in infantile Pompe disease

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2014.12.128 ◽

2015 ◽

Vol 114 (2) ◽

pp. S61

Author(s):

Zoheb Kazi ◽

Katie Berrier ◽

Cheng Lu ◽

Deeksha Bali ◽

J. Will Thompson ◽

...

Keyword(s):

Immune Response ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Pompe Disease ◽

Enzyme Replacement ◽

Infantile Pompe Disease

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The use of port-a-caths in adult patients with Lysosomal Storage Disorders receiving Enzyme Replacement Therapy-one centre experience

Molecular Genetics and Metabolism Reports ◽

10.1016/j.ymgmr.2017.10.003 ◽

2017 ◽

Vol 13 ◽

pp. 111-114 ◽

Cited By ~ 3

Author(s):

Mairead McLoughlin ◽

Karolina M. Stepien ◽

Briony McNelly ◽

Lorraine Thompson ◽

Janet Gorton ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Lysosomal Storage Disorders ◽

Adult Patients ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Storage Disorders

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The NCS-LSD cohort study: a description of the methods and analyses used to assess the long-term effectiveness of enzyme replacement therapy and substrate reduction therapy in patients with lysosomal storage disorders

Journal of Inherited Metabolic Disease ◽

10.1007/s10545-014-9679-6 ◽

2014 ◽

Vol 37 (6) ◽

pp. 939-944 ◽

Cited By ~ 8

Author(s):

W. E. Henley ◽

L. J. Anderson ◽

K. M. Wyatt ◽

V. Nikolaou ◽

R. Anderson ◽

...

Keyword(s):

Cohort Study ◽

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Lysosomal Storage Disorders ◽

Substrate Reduction Therapy ◽

Lysosomal Storage ◽

Enzyme Replacement ◽

Substrate Reduction ◽

Storage Disorders

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Enzyme Replacement Therapy for Genetic Disorders Associated with Enzyme Deficiency

Current Medicinal Chemistry ◽

10.2174/0929867328666210526144654 ◽

2021 ◽

Vol 28 ◽

Author(s):

Marialaura Marchetti ◽

Serena Faggiano ◽

Andrea Mozzarelli

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Rare Diseases ◽

Mammalian Cells ◽

Metabolic Diseases ◽

Genetic Disorders ◽

Life Quality ◽

Lysosomal Storage Diseases ◽

Lysosomal Storage ◽

Enzyme Replacement

: Mutations in human genes might lead to loss of functional proteins, causing diseases. Among these genetic disorders, a large class is associated with the deficiency in metabolic enzymes, resulting in both an increase in the concentration of substrates and a loss in the metabolites produced by the catalyzed reactions. The identification of therapeutic actions based on small molecules represents a challenge to medicinal chemists because the target is missing. Alternative approaches are biology-based, ranging from gene and stem cell therapy, CRISPR/Cas9 technology, distinct types of RNAs, and enzyme replacement therapy (ERT). This review will focus on the latter approach that since the 1990s has been successfully applied to cure many rare diseases, most of them being lysosomal storage diseases or metabolic diseases. So far, a dozen enzymes have been approved by FDA/EMA for lysosome storage disorders and only a few for metabolic diseases. Enzymes for replacement therapy are mainly produced in mammalian cells and some in plant cells and yeasts and are further processed to obtain active, highly bioavailable, less degradable products. Issues still under investigation for the increase in ERT efficacy are the optimization of enzymes interaction with cell membrane and internalization, the reduction in immunogenicity, and the overcoming of blood-brain barrier limitations when neuronal cells need to be targeted. Overall, ERT has demonstrated its efficacy and safety in the treatment of many genetic rare diseases, both saving newborn lives and improving patients’ life quality, and represents a very successful example of targeted biologics.

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