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

Derralynn A Hughes ^1*, Perry M Elliott ², Jaymin Shah ², Jane Zuckerman ³, Gerry Coughlan ³, Jocelyn Brookes ⁴ and Atul B Mehta ³

¹ Royal Free and University College Medical School, United Kingdom
² The Heart Hospital, United Kingdom
³ Royal Free Hospital, United Kingdom
⁴ The Middlesex Hospital, United Kingdom

^* To whom correspondence should be addressed. E-mail: d.hughes{at}medsch.ucl.ac.uk.

Accepted 22 February 2007

Abstract

Background Anderson- Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme -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 six 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 magnetic resonance imaging, 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.

Keywords: Anderson-Fabry, agalsidase alfa, cardiomyopathy, enzyme, lysosomal storage

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Relevant Article

Treatment of Anderson–Fabry disease

Ales Linhart
Heart 2008 94: 138-139. [Extract] [Full Text] [PDF]

This article has been cited by other articles:

• Karamitsos, T. D., Francis, J. M., Myerson, S., Selvanayagam, J. B., Neubauer, S. (2009). The Role of Cardiovascular Magnetic Resonance Imaging in Heart Failure. J Am Coll Cardiol 54: 1407-1424 [Abstract] [Full Text]  
• Mehta, A, Clarke, J T R, Giugliani, R, Elliott, P, Linhart, A, Beck, M, Sunder-Plassmann, G, on behalf of the FOS Investigators, (2009). Natural course of Fabry disease: changing pattern of causes of death in FOS - Fabry Outcome Survey. J. Med. Genet. 46: 548-552 [Abstract] [Full Text]  
• Imbriaco, M, Pisani, A, Spinelli, L, Cuocolo, A, Messalli, G, Capuano, E, Marmo, M, Liuzzi, R, Visciano, B, Cianciaruso, B, Salvatore, M (2009). Effects of enzyme-replacement therapy in patients with Anderson-Fabry disease: a prospective long-term cardiac magnetic resonance imaging study. Heart 95: 1103-1107 [Abstract] [Full Text]  
• Thurberg, B. L., Fallon, J. T., Mitchell, R., Aretz, T., Gordon, R. E., O'Callaghan, M. W. (2009). Cardiac Microvascular Pathology in Fabry Disease: Evaluation of Endomyocardial Biopsies Before and After Enzyme Replacement Therapy. Circulation 119: 2561-2567 [Abstract] [Full Text]  
• West, M., Nicholls, K., Mehta, A., Clarke, J. T.R., Steiner, R., Beck, M., Barshop, B. A., Rhead, W., Mensah, R., Ries, M., Schiffmann, R. (2009). Agalsidase Alfa and Kidney Dysfunction in Fabry Disease. J. Am. Soc. Nephrol. 20: 1132-1139 [Abstract] [Full Text]  
• Weidemann, F., Niemann, M., Breunig, F., Herrmann, S., Beer, M., Stork, S., Voelker, W., Ertl, G., Wanner, C., Strotmann, J. (2009). Long-Term Effects of Enzyme Replacement Therapy on Fabry Cardiomyopathy: Evidence for a Better Outcome With Early Treatment. Circulation 119: 524-529 [Abstract] [Full Text]  
• Kovacevic-Preradovic, T., Zuber, M., Jost, C.H. A., Widmer, U., Seifert, B., Schulthess, G., Fischer, A., Jenni, R. (2008). Anderson-Fabry disease: long-term echocardiographic follow-up under enzyme replacement therapy. Eur J Echocardiogr 9: 729-735 [Abstract] [Full Text]  
• Camici, P. G (2008). Coronary Microvascular Dysfunction in Patients with Cardiomyopathies. Circ Heart Fail 1: 150-152 [Full Text]  
• Linhart, A. (2008). Treatment of Anderson Fabry disease. Heart 94: 138-139 [Full Text]