Haematopoietic cell transplantation (HCT) in combination with enzyme replacement therapy (ERT) in patients with Hurler syndrome

Abstract

Hurler syndrome (MPS 1H) is the severe form of mucopolysaccharidosis type 1 (MPS 1). Haematopoietic cell transplantation (HCT) is the treatment of choice, but carries a high incidence of graft failure and morbidity. The use of enzyme replacement therapy (ERT) might improve the clinical signs and symptoms before HCT, resulting in less transplantation-related complications. Moreover, clearance of glycosaminoglycans (GAG's) from the bone marrow might improve engraftment. Twenty-two patients with MPS 1H received one or more HCT procedures in combination with ERT. One patient with severe cardiomyopathy improved significantly after ERT. All children were in a relatively good clinical condition before HCT. Of patients 59, 82 and 86% were alive and engrafted after one, two and three HCT procedures, respectively. Two patients died after repetitive HCT. No serious ERTinfusion-related toxicity occurred. ERT with HCT was well tolerated. Neither a positive nor a negative effect on the number of patients who are alive and engrafted after receiving ERT before HCT as compared to a historic cohort was noted. However, patients in a poor clinical condition before HCT might benefit from ERT.

Analysis of Glycosaminoglycans in Cerebrospinal Fluid from Patients with Mucopolysaccharidoses by Isotope-Dilution Ultra-Performance Liquid Chromatography–Tandem Mass Spectrometry

“…5 The methylated disaccharide derived from the NA domains of HS behaved similarly to that derived from CS. The presumed dimeric product derived from the NS domain yielded predominantly a sodiated molecular ion at m/z 406 in the mass spectrum of the methanolysate HS (data not shown).…”

Significantly increased lifespan and improved behavioral performances by rAAV gene delivery in adult mucopolysaccharidosis IIIB mice

“…No treatment is currently available for MPS IIIB. The therapies currently available for other MPS disorders, such as bone marrow transplantation 4,5 and recombinant enzyme replacement therapy (ERT), 6,7 are not recommended for MPS III. This is due to the fact that the CNS pathologies in MPS III are global, and neither the peripherally delivered bone marrow stem cells nor the recombinant enzymes can be efficiently delivered to the CNS through the blood-brain barrier (BBB).…”

Combined Enzyme Replacement Therapy and Hematopoietic Stem Cell Transplantation in Mucopolysacharidosis Type VI

“…Supplementary ERT before HSCT rapidly reduces upper airway obstruction, and improves cardiorespiratory capacity thereby improving patient fitness for HSCT (Grewal et al 2005;Cox-Brinkman et al 2006;Muenzner et al 2009;Wynn et al 2009;Tolar et al 2008;Bijarnia et al 2009;Clarke et al 2009). We have demonstrated that a treatment regimen of ERT combined with HSCT in our patient with MPS VI provided similar benefit.…”