Treatment with pentosan polysulphate in patients with MPS I: results from an open label, randomized, monocentric phase II study

Abstract

Current treatment options for MPS I have limited effects on some organs, including the skeletal system. In MPS animal models pentosan polysulphate (PPS) reduces the concentrations of glycosaminoglycans (GAGs) in tissues and body fluids and improves cartilaginous and osseous pathologies. The goals of this study were to investigate primarily the safety and secondary the clinical effects, concerning mobility and pain, of PPS treatment in MPS I patients. Four MPS I-Hurler-Scheie/-Scheie patients aged 35.6 ± 6.4years with one male were included in the study. All patients were on enzyme replacement therapy since 9.45 ± 3.75years. PPS was applied subcutaneously in two patients with 1mg/kg and in two patients with 2mg/kg, weekly for 12weeks and then biweekly for 12weeks. The 24-week treatment with PPS was well tolerated by all patients. Urinary GAG concentrations were reduced from 4.13 ± 1.17 at baseline to 2.69 ± 0.36mg/mmol creatinine after 24-week treatment with 1mg/kg PPS, and from 6.71 ± 0.62 to 2.65 ± 0.09mg/mmol creatinine with 2mg/kg PPS. An improvement in range of motion was noted in three out of four patients. The pain intensity score was reduced from 4.5 ± 1.77 at baseline to 1.8 ± 0.47 after 24-week treatment with 1mg/kg PPS; patients with 2mg/kg PPS already had minimal pain at the start of the study. In conclusion, PPS treatment in a small number of adult MPS I patients was well tolerated and resulted in a significant reduction of urinary GAG excretion and in an improvement of joint mobility and pain.