Enzyme replacement therapy in Fabry disease

Background/objectives. Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the gene encoding alpha-galactosidase A, an enzyme involved in lipid metabolism. The activity of alpha-galactosidase is reduced or lacking in Fabry disease leading to accumulation of glycosphingolipids in virtually all organs of the human body and to progressive organ dysfunction. Without enzyme replacement, the average life expectancy is limited to 50 years in men and to 70 years in women. Material and methods. In Europe two different enzyme preparations, agalsidase alfa and agalsidase beta, are approved for the treatment of Fabry disease. Both compounds differ in the manufacturing process, the antigenicity and dosing. Enzyme replacement therapy (ERT) is costly; therefore, in 2013 the Association of the Scientific Medical Societies in Germany (AWMF) published guidelines for diagnosis and therapy of Fabry disease defining criteria for when ERT should be initiated. Results. A number of open label studies, uncontrolled observations, a limited number of placebo-controlled clinical trials and valuable data from registries have demonstrated an ERT-associated reduction in neuropathic pain, gastrointestinal symptoms, slowing of renal function loss as well as slower progression of heart disease and an improvement in quality of life. Conclusion. Whether prolongation of life of patients with this severe diasease will be achieved and whether there are differences between the two enyme preparations with respect to clinical endpoints, such as the prevention of heart failure, stroke and death through ERT has not been demonstrated in randomized controlled clinical trials yet.