A randomized, double-blind, placebo-controlled trial and an open-label extension study evaluated the safety and efficacy of recombinant human alpha-galactosidase A (agalsidase beta) in patients with Fabry's disease. The study included 58 patients with classic Fabry's disease, who were treated every two weeks for 20 weeks. After the double-blind phase, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy endpoint was the clearance of globotriaosylceramide (GL3) microvascular endothelial deposits in renal biopsies. After 20 weeks, 69% of patients in the recombinant alpha-galactosidase A group had no GL3 deposits, compared to none in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had reduced GL3 deposits in the skin and heart. Plasma GL3 levels were directly correlated with the clearance of microvascular deposits. After six months of open-label therapy, all patients who had biopsies had clearance of GL3 deposits. Mild-to-moderate infusion reactions were more common in the recombinant alpha-galactosidase A group. The study also assessed the clearance of GL3 in heart and skin tissues, as well as changes in pain and quality of life. Patients in the recombinant alpha-galactosidase A group showed significant improvements in physical role and emotional role scores on the SF-36 questionnaire. The open-label extension study confirmed the results of the double-blind study, showing that GL3 deposits were cleared or further reduced in all three tissue types. The percentage of patients with cleared GL3 deposits in the endomyocardium increased from 67% to 82% after six months of treatment. The study demonstrated that recombinant alpha-galactosidase A replacement therapy effectively cleared GL3 deposits in the kidneys, heart, and skin, reversing the pathogenesis of the main clinical manifestations of Fabry's disease. The results suggest that plasma GL3 levels may be a non-invasive indicator of systemic substrate clearance. The study was supported by grants from the National Institutes of Health and Genzyme Corporation. Dr. Desnick has received grant support from and serves as a consultant to Genzyme. The study was conducted at multiple sites, with contributions from numerous investigators, pathologists, and specialists. The study highlights the effectiveness of recombinant alpha-galactosidase A in treating Fabry's disease and the importance of continued treatment to reduce glycosphingolipid deposition in other cell types.A randomized, double-blind, placebo-controlled trial and an open-label extension study evaluated the safety and efficacy of recombinant human alpha-galactosidase A (agalsidase beta) in patients with Fabry's disease. The study included 58 patients with classic Fabry's disease, who were treated every two weeks for 20 weeks. After the double-blind phase, all patients received recombinant alpha-galactosidase A in an open-label extension study. The primary efficacy endpoint was the clearance of globotriaosylceramide (GL3) microvascular endothelial deposits in renal biopsies. After 20 weeks, 69% of patients in the recombinant alpha-galactosidase A group had no GL3 deposits, compared to none in the placebo group (P<0.001). Patients in the recombinant alpha-galactosidase A group also had reduced GL3 deposits in the skin and heart. Plasma GL3 levels were directly correlated with the clearance of microvascular deposits. After six months of open-label therapy, all patients who had biopsies had clearance of GL3 deposits. Mild-to-moderate infusion reactions were more common in the recombinant alpha-galactosidase A group. The study also assessed the clearance of GL3 in heart and skin tissues, as well as changes in pain and quality of life. Patients in the recombinant alpha-galactosidase A group showed significant improvements in physical role and emotional role scores on the SF-36 questionnaire. The open-label extension study confirmed the results of the double-blind study, showing that GL3 deposits were cleared or further reduced in all three tissue types. The percentage of patients with cleared GL3 deposits in the endomyocardium increased from 67% to 82% after six months of treatment. The study demonstrated that recombinant alpha-galactosidase A replacement therapy effectively cleared GL3 deposits in the kidneys, heart, and skin, reversing the pathogenesis of the main clinical manifestations of Fabry's disease. The results suggest that plasma GL3 levels may be a non-invasive indicator of systemic substrate clearance. The study was supported by grants from the National Institutes of Health and Genzyme Corporation. Dr. Desnick has received grant support from and serves as a consultant to Genzyme. The study was conducted at multiple sites, with contributions from numerous investigators, pathologists, and specialists. The study highlights the effectiveness of recombinant alpha-galactosidase A in treating Fabry's disease and the importance of continued treatment to reduce glycosphingolipid deposition in other cell types.