Current
therapies for the
mucopolysaccharidoses (MPS) do not effectively address skeletal and
neurological manifestations.
Pentosan polysulfate (PPS) is an alternative treatment strategy that has been shown to improve bone architecture, mobility, and
neuroinflammation in MPS animals. The aims of this study were to a) primarily establish the safety of weekly PPS
injections in attenuated MPS II, b) assess the efficacy of treatment on MPS pathology, and c) define appropriate clinical endpoints and
biomarkers for future clinical trials.
Subcutaneous injections were administered to three male Japanese patients for 12 weeks.
Enzyme replacement therapy was continued in two of the patients while they received PPS and halted for two months in one patient before starting PPS. During treatment, one patient experienced an elevation of
alanine transaminase, and another patient experienced convulsions; however, these incidences were non-cumulative and unrelated to PPS administration, respectively. Overall, the
drug was well-tolerated in all patients, and no serious
drug-related adverse events were noted. Generally, PPS treatment led to an increase in several parameters of shoulder range of motion and decrease of the inflammatory
cytokines, MIF and TNF-α, which are potential clinical endpoints and
biomarkers, respectively. Changes in urine and serum
glycosaminoglycans were inconclusive. Overall, this study demonstrates the safety of using PPS in adults with MPS II and suggests the efficacy of PPS on MPS pathology with the identification of potential clinical endpoints and
biomarkers.