Immune response hinders therapy for lysosomal storage diseases.
Enzyme replacement therapy (ERT) for the lysosomal storage disease mucopolysaccharidosis I (MPS I) involves i.v. injection of alpha-l-iduronidase, which can be taken up by cells throughout the body. While a significant immune response to ERT has been shown in patients with MPS I, little is known about what effect anti-enzyme antibodies have on treatment efficacy. In this issue of the JCI, Dickson et al. demonstrate that anti-enzyme antibodies inhibit enzyme uptake and substantially limit the therapeutic efficacy of ERT in canines with MPS I (see the related article beginning on page 2868). Furthermore, the induction of immune tolerance--via oral delivery of cyclosporine A and azathioprine for two months at the time of initiation of ERT with recombinant human alpha-L-iduronidase--improved enzyme uptake in organs. Therefore, transient immunosuppression may enhance ERT for lysosomal storage diseases.
Ponder
Katherine P
KP
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA. KPONDER@DOM.WUSTL.EDU
D000818:Animals; D000906:Antibodies / Q000276:immunology*; D001379:Azathioprine / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004285:Dogs; D007068:Iduronidase / Q000627:therapeutic use*; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016464:Lysosomal Storage Diseases / Q000188:drug therapy* / Q000473:pathology; D018448:Models, Immunological; D008059:Mucopolysaccharidosis I / Q000188:drug therapy* / Q000473:pathology; D013997:Time Factors
D000906:Antibodies; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007068:Iduronidase; D001379:Azathioprine