Enzyme reconstitution/replacement therapy for lysosomal storage disease

Division of Human Genetics, Cincinnati Children's Hospital Medical Center and the Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45229-3039, USA.
Current Opinion in Pediatrics (Impact Factor: 2.53). 01/2008; 19(6):628-35. DOI: 10.1097/MOP.0b013e3282f161f2
Source: PubMed


Over the past 15 years, the lysosomal storage diseases have become paradigms for the specific treatment of monogenic disorders, particularly those affecting children. This review summarizes the phenotypes and recent literature regarding enzyme reconstitution (replacement) therapy and outcomes for such treatable lysosomal storage diseases: Gaucher disease, Fabry disease, Pompe disease and the mucopolysaccharidoses.
Recent clinical trials have shown that enzyme reconstitution therapy effectively treats many of the manifestations of the lysosomal storage diseases. When initiated early in the disease course, enzyme reconstitution therapy can reverse some disease manifestations, but may not completely alleviate the disease progression. Enzyme reconstitution therapy is generally well tolerated. Many adverse events are antibody-related, but can be managed without requiring cessation of enzyme reconstitution therapy. Documented IgE reactions, i.e. anaphylactoid, are quite rare (fewer than 1%).
Enzyme reconstitution therapy is a safe and effective treatment modality available for several of the lysosomal storage diseases. Owing to the short history of enzyme reconstitution therapy, the long-term outcomes of enzyme reconstitution therapy-treated individuals are unknown and require further investigation. Medical professionals must learn to identify patients likely to benefit from these life-changing therapies so as to prevent many of the devastating, irreversible complications of the lysosomal storage diseases.

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    • "It is important to remember that ERT is a treatment with partial effects in specific body compartments [19]. Although it can be a life-lengthening therapeutic measure, it does not seem to alter the natural history of the skeletal disorder in MPS II and children will still endure the skeletal changes of the disease. "
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    ABSTRACT: Mucopolysaccharidosis type II (MPS II; Hunter syndrome) is an X-linked, recessive, lysosomal storage disorder caused by deficiency of iduronate-2-sulfatase. Early bone involvement leads to decreased growth velocity and short stature in nearly all patients. Our analysis aimed to investigate the effects of enzyme replacement therapy (ERT) with idursulfase (Elaprase) on growth in young patients with mucopolysaccharidosis type II. Analysis of longitudinal anthropometric data of MPS II patients (group 1, n = 13) who started ERT before 6 years of age (range from 3 months to 6 years, mean 3.6 years, median 4 years) was performed and then compared with retrospective analysis of data for MPS II patients naïve to ERT (group 2, n = 50). Patients in group 1 received intravenous idursulfase at a standard dose of 0.58 mg/kg weekly for 52-288 weeks. The course of average growth curve for group 1 was very similar to growth pattern in group 2. The average value of body height in subsequent years in group 1 was a little greater than in group 2, however, the difference was not statistically significant. In studied patients with MPS II, idursulfase did not appear to alter the growth patterns.
    Full-text · Article · Jan 2014 · PLoS ONE
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    • "It should be noted that a high level of antibody response to ERT has been observed in other lysosomal storage disorders including MPS I, II, and VI. In the majority of cases, available evidence has not demonstrated a correlation between antibody development and changes in safety or efficacy [27]. "
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    ABSTRACT: This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT) in patients with mucopolysaccharidosis (MPS) IVA. Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS) levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance. Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a), matrix metalloprotein (MMP)-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P. Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a), and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.
    Full-text · Article · Dec 2011 · Orphanet Journal of Rare Diseases
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    • "Cardiac disease is particularly prominent in lysosomal glycogen storage diseases (Pompe and Danon disease), MPSs and in glycosphingolipidoses (Fabry disease). Among lysosomal storage disorders, enzyme replacement therapy for the treatment of Gaucher disease, Pompe disease, Fabry disease and MPS I, II and VI has been approved in the United States.6) "
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    ABSTRACT: In the absence of hypertension, hypertrophic cardiomyopathy is the most common cause of left ventricular hypertrophy (LVH). However, it has been reported that up to 3% of males with unexplained LVH have Fabry disease, an X-linked disorder of glycophospholipid metabolism that is due to a deficiency in the lysosomal enzyme alpha-galactosidase A (alpha-Gal A). A 44-year-old man was admitted to our hospital with palpitations. He had a history of chronic renal failure diagnosed at age 33 followed by kidney transplantation performed at our institution 2 years later, as well as long-standing hypohidrosis. His medications included prednisolone (5 mg daily), mycophenolate mofetil (1,000 mg, bid), and cyclosporine (150 mg, bid). On hospital day two, an echocardiogram demonstrated increased left ventricular wall thickness (septal wall thickness of 28 mm, posterior wall thickness of 20 mm). Diastolic dysfunction was noted on transmitral flow patterns and tissue Doppler imaging. The patient was found to have low plasma alpha-Gal A activity. A previously reported H46R missense mutation was detected in his alpha-Gal A gene and the patient was subsequently diagnosed with Fabry disease.
    Full-text · Article · Aug 2009 · Korean Circulation Journal
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