Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa

Hughes, D. A.; Elliott, P. M.; Shah, J.; Zuckerman, J.; Coghlan, G.; Brookes, J.; Mehta, A. B.
February 2008
Heart;Feb2008, Vol. 94 Issue 2, p153
Academic Journal
Background: Anderson-Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme α-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb3) in the lysosomes of cells throughout the body that ultimately results in premature death from renal, cardiac or cerebrovascular complications. Until recently, there was no effective therapy available for this disease. The present study was designed to assess the safety and efficacy of enzyme replacement therapy with agalsidase alfa on the cardiac manifestations of Anderson-Fabry disease. Method: The effects of therapy with agalsidase alfa on cardiac structure and function were assessed in a randomised, double-blind, placebo-controlled study of 15 adult male patients with Anderson-Fabry disease. The following parameters were measured at baseline and 6 months: left ventricular mass, QRS duration and levels of Gb3 in cardiac tissue, urine sediment and plasma. After 6 months of the randomised trial patients were enrolled in a 2-year open-label extension study. Results: Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p = 0.041). A mean 20% reduction in myocardial Gb3 content as assessed by serial transvenous endomyocardial biopsies was demonstrated over the 6 months of enzyme replacement compared to a mean 10% increase in patients receiving placebo (p = 0.42) Conclusion: Enzyme replacement therapy with agalsidase alfa resulted in regression of the hypertrophic cardiomyopathy associated with Anderson-Fabry disease.


Related Articles

  • Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy. Kovacevic-Preradovic, T.; Zuber, M.; Jost, C. H. Attenhofer; Widmer, U.; Seifert, B.; Schulthess, G.; Fischer, A.; Jenni, R. // European Journal of Echocardiography;Nov2008, Vol. 9 Issue 6, p729 

    Aims: Anderson-Fabry disease affects various organ systems due to glycosphingolipid accumulation. Enzyme replacement therapy (ERT) has been reported to decrease left ventricular wall thickening (LVWT) and to improve diastolic dysfunction.

  • Sfingolipit depo hastalıklarında enzim inhibitörlerinin tedavide kullanımları. Sinici, İncilay // Cocuk Sagligi ve Hastaliklari Dergisi;jul-sep2010, Vol. 53 Issue 3, p236 

    Sphingolipidoses are a group of inherited metabolic diseases caused by a genetic defect in the catabolism of sphingosine-containing lipids. Glycosphingolipids accumulate in the lysosome due to a mutation in genes that encode their catabolic enzymes or activator proteins. They are fatal disorders...

  • Treatment of Anderson-Fabry disease. Linhart, Ales // Heart;Feb2008, Vol. 94 Issue 2, p138 

    The article focuses on the efficacy of enzyme replacement therapy (ERT) for the treatment of Anderson-Fabry disease (AFD). AFD is described as an X-linked, metabolic disorder characterized by a defect in the degradation of glycosphingolipids. The cause involves the mutation in the gene encoding...

  • Extracorporeal Enzyme Reactors for Depletion of Phenylalanine in Phenylketonuria. Ambrus, Clara M.; Anthone, Sidney; Horvath, Csaba; Kalghatgi, Krishna; Lele, Amol S.; Eapen, Giorgina; Ambrus, Julian L.; Ryan, A. John; Li, Philip // Annals of Internal Medicine;Apr87, Vol. 106 Issue 4, p531 

    Presents a study that developed multitubular enzyme reactors with immobilized enzymes to achieve depletion of circulating substrate by extracorporeal means. Background on the effect of excess substrate accumulation on the clinical manifestations of metabolic diseases; Details on the application...

  • ADRENOLEUKODYSTROPHY - CASE REPORT. Galesanu, Corina; Lisnic, Natalia; Branisteanu, D.; Moisii, Liliana; Tache, Cristina; Diaconu, Georgeta; Rusu, Cristina // Acta Endocrinologica (1841-0987);Jul-Sep2005, Vol. 1 Issue 3, p359 

    Adrenoleukodystrophy (ALD) is a hereditary metabolic disease X-linked (Xq28) with autosomal recessive traits, secondary to a mutation in the ABCD1 gene. The case of a boy aged 7 years and 10 months admitted for vision disturbances, muscle weakness, balance disturbances and spastic paraparesis is...

  • Cardiomyopathy and Response to Enzyme Replacement Therapy in a Male Mouse Model for Fabry Disease. Cat, Aurelie Nguyen Dinh; Escoubet, Brigitte; Agrapart, Vincent; Griol-Charhbili, Violaine; Schoeb, Trenton; Feng, Wenguang; Jaimes, Edgar; Warnock, David G.; Jaisser, Frederic // PLoS ONE;May2012, Vol. 7 Issue 5, p1 

    Fabry disease is an X-linked disorder of glycosphingolipid metabolism that results in progressive accumulation of neutral glycosphingolipids, (predominately globotriaosylceramide; GL-3) in lysosomes, as well as other cellular compartments and the extracellular space. Our aim was to characterize...

  • Diffuse structural and metabolic brain changes in Fabry disease. Marino, Silvia; Borsini, Walter; Buchner, Susanna.; Mortilla, Marzia; Stromillo, Maria L; Battaglini, Marco; Giorgio, Antonio; Bramanti, Placido; Federico, Antonio; De Stefano, Nicola // Journal of Neurology;Apr2006, Vol. 253 Issue 4, p434 

    Objective: To assess structural and metabolic brain changes in subjects affected by Fabry disease (FD) or carrying the disease mutation. Background: FD is an X-linked metabolic disorder due to α-galactosidase A deficiency, which leads to storage of glycosphingolipids in many tissues and...

  • Fabry's disease.  // Taber's Cyclopedic Medical Dictionary;2005, p770 

    A definition of the medical term "Fabry's disease" is presented. Fabry's disease is a recessive metabolic disease in which there is a galactosidase deficiency. It leads to accumulation of glycosphingolipids throughout the body. As patients with the disease age, glycolipid deposition in the...

  • New approaches towards laboratory diagnosis of isolated sulphite oxidase deficiency. Sass, Jörn Oliver; Nakanishi, Toyofumi; Sato, Takako; Shimizu, Akira // Annals of Clinical Biochemistry;Mar2004, Vol. 41 Issue 2, p157 

    Background: Molybdenum cofactor deficiency (resulting in combined deficiencies of the enzymes sulphite oxidase, xanthine dehydrogenase and aldehyde dehydrogenase) and isolated sulphite oxidase deficiency are inherited metabolic diseases which follow an autosomal recessive trait of inheritance....


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics