Replacement therapy in Mucopolysaccharidosis type VI: advantages of early onset of therapy

Intrathecal recombinant human 4-sulfatase reduces accumulation of glycosaminoglycans in dura of mucopolysaccharidosis VI cats

“…The A/0 and A/V6 cats exhibited a moderate degree of generalized epiphyseal dysplasia and osteopenia, with degenerative joint disease resembling the radiographical abnormalities observed in young, untreated MPS-VI cats (10,11). Similarly, the radiographic improvements seen in eight A/E6 cats at the end of the study were comparable to those reported in young IV-ERT MPS-VI cats treated from birth (10,11).…”

“…The A/0 and A/V6 cats exhibited a moderate degree of generalized epiphyseal dysplasia and osteopenia, with degenerative joint disease resembling the radiographical abnormalities observed in young, untreated MPS-VI cats (10,11). Similarly, the radiographic improvements seen in eight A/E6 cats at the end of the study were comparable to those reported in young IV-ERT MPS-VI cats treated from birth (10,11). Although the dimensions and shape of most long bones and lumbar vertebrae were improved in the A/E6 cats as compared with A/V6 and A/0 cats, no skeletal disease features were completely normalized.…”

“…In the MPS-VI cat, IV-ERT from birth effectively improves pathology in various tissues, including heart valves, aorta, bones, liver, and kidney (10,11). Although articular cartilages do not benefit from intravenously administered rhASB due to their avascular nature, they nevertheless show significant improvement when rhASB is injected directly into the joint spaces (12,13).…”

“…Although articular cartilages do not benefit from intravenously administered rhASB due to their avascular nature, they nevertheless show significant improvement when rhASB is injected directly into the joint spaces (12,13). Similarly, neuroparenchyma outside the blood-brain barrier does not benefit from recombinant enzyme administered systemically at a standard dose, with vacuolation evident in dura mater of MPS-VI cats treated weekly with 1 or 2 mg/kg rhASB from birth to 6 months of age (11). In a pilot study using mature MPS-VI cats tolerant to rhASB, a short course of Articles Auclair et al…”

Inherited metabolic disease in companion animals: Searching for nature’s mistakes

“…These animals have a similar clinical presentation and pathogenesis as the human diseases. The discovery of naturally occurring models of lysosomal storage diseases has enabled the development and assessment of efficacy and safety of enzyme replacement therapy and gene therapy approaches (Auclair et al, 2003;Casal and Haskins, 2005;Ellinwood et al, 2006;Crawley et al, 1996;Ponder et al, 2002). This has paved the way for therapy of the human disease.…”