Dose responsive effects of subcutaneous pentosan polysulfate injection in mucopolysaccharidosis type VI rats and comparison to oral treatment

Frohbergh M, Ge Y, Meng F, Karabul N, Solyom A, Lai A, Iatridis J, Schuchman EH, Simonaro CM · PLoS One

Once-weekly injection matched or beat daily oral dosing on every shared endpoint and added several the oral route did not reach — glycosaminoglycan clearance from urine and tissues, rotarod endurance, and articular cartilage and bone improvements at some doses. The optimum was 2 mg/kg subcutaneously, the same per-kilogram dose used in the human injection trials. No coagulation or liver abnormalities appeared over six months.

Population

One-month-old mucopolysaccharidosis type VI rats treated for 6 months

Intervention

Weekly subcutaneous PPS at human-equivalent 1, 2 and 4 mg/kg

Comparator

Daily oral PPS at human-equivalent 4 mg/kg

Limitations

Rat model of a genetic storage disease; the cartilage findings are secondary and were not consistent across dose groups; the authors' premise that injected PPS has higher bioavailability than oral is asserted from prior work rather than measured here.