Pentosan Polysulfate: Oral Versus Subcutaneous Injection in Mucopolysaccharidosis Type I Dogs

Simonaro CM, Tomatsu S, Sikora T, Kubaski F, Frohbergh M, Guevara JM, Wang RY, Vera M, Kang JL, Smith LJ, Schuchman EH, Haskins ME · PLoS One

A head-to-head of the two routes at matched dose in a large animal. Both cut inflammatory cytokines and tissue glycosaminoglycan storage and improved arterial pathology, but the reductions were most evident after subcutaneous dosing, and only the subcutaneous route significantly lowered cytokines in cerebrospinal fluid. No liver-enzyme or coagulation abnormalities appeared on either route over a year or more.

Population

Dogs with mucopolysaccharidosis type I, five per group, treated from 3 weeks of age

Intervention

Daily oral PPS for 17 months or subcutaneous PPS once every two weeks for 12 months, both at a human-equivalent 1.6 mg/kg

Comparator

Untreated MPS I dogs

Limitations

A lysosomal storage disease model, not osteoarthritis; endpoints are arterial and biochemical; five dogs per group. The authors attribute the route difference to bioavailability of roughly 15% subcutaneous against under 2% oral, on unpublished manufacturer data; two authors hold a patent application on anti-TNF therapy for these diseases; PPS supplied by bene.