Mol Genet Metab 2010 Dec 1;101(4):346-8. Epub 2010 Aug 1.
Gene Therapy Center, Department of Pediatrics, Institute of Human Genetics, University of Minnesota, Minneapolis, MN, USA.
Background: Maroteaux-Lamy syndrome, or mucopolysaccharidosis (MPS) type VI, is the autosomal recessive lysosomal disorder resulting from deficient N-acetylgalactosamine 4-sulfatase (ARSB) and the consequent accumulation of glycosaminoglycan (GAG). Patients fully engrafted after hematopoietic stem cell transplantation (HSCT) demonstrate several indicators of metabolic correction such as reduction in liver size, absence of hepatic ultrastructural pathology, and patients do not develop cervical cord compression. Engrafted patients demonstrate reduction in urine GAG achieving near-normal levels.
Hypothesis: We presumed that HSCT engraftment from a normal individual would provide sufficient systemic enzyme to accomplish maximal metabolic correction, and that no additional benefit would accrue from additional therapy such as with intravenous recombinant human ARSB protein, galsulfase.
Materials And Methods: A 22-year-old male had received an allogeneic bone marrow transplant from an HLA-identical sibling donor, and remained fully engrafted after 20 years. In response to his request regarding the potential benefit of enzyme replacement therapy, we administered a single, standard dose of galsulfase while monitoring urine GAG daily, before and after the treatment.
Results: Urine GAG declined from slightly high pre-treatment levels (7.63 mg GAG/mmol creatinine; range 7.0-8.5, N=3) progressively declining below the age-specific normal range (<6.5) over 10 days to the lowest level of 4.4, with a mean post-treatment level of 5.60 (N=10).
Conclusions: Somewhat surprisingly, the biomarker urine GAG was significantly reduced after a single treatment of intravenous galsulfase thus suggesting that supplemental enzyme replacement therapy might improve the clinical outcome for donor-engrafted patients with MPS VI.