title: Enzyme replacement therapy in Fabry disease.
abstract: Recent clinical trials have demonstrated that enzyme replacement therapy with alpha-galactosidase A (alpha-Gal A) constitutes a major clinical advance in the treatment of patients with Fabry disease. This new therapeutic approach has been shown to be well tolerated and effective in reducing levels of the storage product globotriaosylceramide and in normalizing many of the debilitating manifestations of the disorder. A double-blind placebo-controlled trial in 26 hemizygous male patients showed that agalsidase alfa (human alpha-Gal A) significantly reduced neuropathic pain (p = 0.02), increased creatinine clearance (p = 0.02), improved glomerular histology, reduced the QRS interval on electrocardiography and increased weight gain. Positron emission tomography also revealed normalization of cerebrovascular flow. After the 6-month controlled period, all patients were given agalsidase alfa for a further 12 months. At the end of this period, all patients had a decrease in neuropathic pain, and there was a significant improvement in their ability to sense heat and cold. In addition, renal function stabilized, even in patients with renal insufficiency at the onset of treatment, and patients reported a normalization of sweating and improvements in their level of energy and sense of well-being. These findings show that enzyme replacement therapy offers promise as an effective management strategy for patients with Fabry disease.
authors.affiliation: Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1260, USA. bradyr@ninds.nih.gov
authors.forename: R O
authors.initials: RO
authors.lastname: Brady
authors.forename: G J
authors.initials: GJ
authors.lastname: Murray
authors.forename: D F
authors.initials: DF
authors.lastname: Moore
authors.forename: R
authors.initials: R
authors.lastname: Schiffmann
mesh_terms: D000818:Animals; D002986:Clinical Trials as Topic; D000795:Fabry Disease / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000627:therapeutic use; D000519:alpha-Galactosidase / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D000519:alpha-Galactosidase