Enzyme replacement therapy in Fabry disease

Recent clinical trials have demonstrated that enzyme replacement therapy wi th alpha -galactosidase A (alpha -Gal A) constitutes a major clinical advan ce in the treatment of patients with Fabry disease. This new therapeutic ap proach has been shown to be well tolerated and effective in reducing levels of the storage product globo-triaosylceramide and in normalizing many of t he debilitating manifestations of the disorder. A double-blind placebo-cont rolled trial in 26 hemizygous male patients showed that agalsidase alfa (hu man alpha -Gal A) significantly reduced neuropathic pain (p = 0.02), increa sed creatinine clearance (p = 0.02), improved glomerular histology, reduced the QRS interval on electrocardiography and increased weight gain. Positro n emission tomography also revealed normalization of cerebrovascular flow. After the 6-month controlled period, all patients were given agalsidase alf a for a further 12 months. At the end of this period, all patients had a de crease in neuropathic pain, and there was a significant improvement in thei r ability to sense heat and cold. In addition, renal function stabilized, e ven in patients with renal insufficiency at the onset of treatment, and pat ients reported a normalization of sweating and improvements in their level of energy and sense of well-being. These findings show that enzyme replacem ent therapy offers promise as an effective management strategy for patients with Fabry disease.