Post-transplant laronidase augmentation for children with Hurler syndrome: biochemical outcomes

Abstract

Allogeneic hematopoietic cell transplantation (HCT) benefits children with Hurler syndrome (MPS-IH). However, survivors remain burdened by substantial MPS-IH related residual disease. We studied the feasibility, safety and biochemical impact of augmentative recombinant intravenous enzyme replacement therapy (IV-ERT) post transplantation. Ten children with MPS-IH and ≥2 years from successful HCT underwent IV-ERT for 2 years’ duration. Patients were monitored for anti-drug antibody (ADA) development, including inhibitory capacity and changes in urinary excretion of glycosaminoglycans (uGAG). Three patients demonstrated low-level ADA at baseline, though all children tolerated IV-ERT well. Eight patients developed ADA over the 2-year study, with 3 (38%) meeting criteria for an inhibitory ADA response. The aggregate cohort experienced a reduction in uGAG from baseline to study end, which was enhanced in children with low or no ADA response. Conversely, children with inhibitory ADA showed increase in uGAG over time. IV-ERT in previously transplanted children with MPS-IH appears safe and can reduce uGAG, although this is reversed by the presence of inhibitory ADA. These data show a biochemical change after initiation of post-HCT IV-ERT, but the occurrence of ADA and inhibitory antibodies are a concern and should be monitored in future efficacy trials. This trial was registered at www.clinicaltrials.gov, NCT01173016, 07/30/2010.