Mucopolysaccharide storage disorders are caused by the deficiency of specific
lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs) such
as chondroitin 4-sulfate and dermatan sulfate. Mucopolysaccharidosis VI (MPS VI,
Maroteaux-Lamy syndrome) is characterized by the absence or marked reduction
in N-acetylgalactosamine 4-sulfatase. The sulfatase activity deficiency results in the
accumulation of the GAG substrate dermatan sulfate throughout the body. This
accumulation leads to widespread cellular, tissue, and organ dysfunction.In clinical studies, 1 mg/kg
galsufase once-weekly for 24 weeks significantly increased baseline-adjusted mean
12 min walk distance compared to placebo, the study’s primary endpoint (+92 m;
p=0.025). A positive, non-significant trend was observed in increasing performance
in a 3 min stair climb test, vs. placebo (+5.7 stairs/min; p=0.053). Additionally,
patients receiving galsulfase showed significant reductions in urinary GAG
secretion compared to placebo, although these reductions were not sufficient to
reach normal, healthy-patient levels. Adverse events associated with the use of
galsulfase included abdominal pain, ear pain, chest pain, conjunctivitis, dyspnea,
and pharyngitis.
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