Enzyme Replacement Therapy for Fabry Disease

摘要

Fabry disease is a rare X-linked disease caused by the deficiency of ???±-galactosidase that leads to the accumulation of abnormal glycolipid. Untreated patients develop potentially lethal complications by age 30 to 50 years. Enzyme replacement therapy is the current standard of therapy for Fabry disease. Two formulations of recombinant human ???±-galactosidase A (agalsidase) are available in most markets: agalsidase-???± and agalsidase-???2, allowing a choice of therapy. However, the US Food and Drug Administration rejected the application for commercialization of agalsidase-???±. The main difference between the 2 enzymes is the dose. The label dose for agalsidase-???± is 0.2 mg/kg/2 weeks, while the dose for agalsidase-???2 is 1.0 mg/kg/2 weeks. Recent evidence suggests a dose-dependent effect of enzyme replacement therapy and agalsidase-???2 is 1.0 mg/kg/2 weeks, which has been shown to reduce the occurrence of hard end points (severe renal and cardiac events, stroke, and death). In addition, patients with Fabry disease who have developed tissue injury should receive coadjuvant tissue protective therapy, together with enzyme replacement therapy, to limit nonspecific progression of the tissue injury. It is likely that in the near future, additional oral drugs become available to treat Fabry disease, such as chaperones or substrate reduction therapy.