A new peer-reviewed study published in PLOS One has provided evidence that pentosan polysulfate sodium (PPS) delivers sustained clinical, functional, and structural benefits in osteoarthritis, reinforcing its potential as a disease-modifying therapy.
The research, supported by Paradigm Biopharmaceuticals (ASX:PAR) and conducted in collaboration with the University of Melbourne, evaluated PPS in companion dogs with naturally occurring osteoarthritis. This is a model widely regarded as one of the most clinically relevant analogues of human joint disease.
Unlike surgically induced or laboratory-based models, the study focused on dogs with established, radiographically confirmed osteoarthritis of the stifle and/or elbow joints. These animals presented with clear clinical pain and functional impairment at baseline, closely mirroring the progressive, age-related pathology seen in human osteoarthritis. Following a six-week course of subcutaneous PPS administered once weekly, the dogs were monitored for a further 26 weeks, allowing investigators to assess not only short-term symptom relief but also the durability of effect over time.
The results demonstrated a clear and sustained reduction in chronic pain among PPS-treated dogs. After adjusting for higher baseline pain scores in the treatment group, investigators found that pain, measured using the Helsinki Chronic Pain Index, continued to improve through the six-month follow-up. In contrast, dogs receiving a placebo experienced a gradual worsening of pain over the same period. These findings were complemented by objective gait analysis, which showed progressive normalisation of gait symmetry and improved weight-bearing in PPS-treated animals.
Importantly, the benefits of PPS extended beyond symptoms and function. Quantitative MRI analysis revealed stabilisation and, in some cases, modest increases in total cartilage volume in treated dogs at both interim and six-month assessments. Placebo-treated dogs, by comparison, continued to show cartilage loss. This divergence provides imaging evidence suggestive of a structural, disease-modifying effect rather than simple symptomatic relief.
Biomarker analyses further supported this interpretation. PPS treatment was associated with reductions in serum CTX-I, a marker of bone resorption, with a statistically significant treatment effect observed at six months. Levels of hyaluronic acid, commonly associated with synovial inflammation and osteoarthritis progression, also declined in treated dogs, consistent with reduced inflammatory joint activity. In parallel, increases in TIMP-1, an endogenous inhibitor of cartilage-degrading enzymes, pointed toward a chondroprotective mechanism of action. Taken together, these biomarker changes aligned with slowed cartilage degradation and altered bone and cartilage turnover.
The study also demonstrated a favourable safety profile. PPS was well tolerated throughout the trial, with no treatment-related adverse events and no clinically meaningful abnormalities observed in hematology or biochemistry assessments.
From a translational perspective, the significance of these findings lies in the natural history of canine osteoarthritis. Because the disease progresses more rapidly in dogs than in humans, a 26-week observation period is considered broadly analogous to multiple years of human disease progression. As such, the sustained clinical, structural, and biomarker effects observed in this study provide a compressed view of longer-term outcomes that are difficult to capture within early-phase human trials.
Crucially, the canine data align closely with outcomes previously reported in Paradigm’s Phase 2 human osteoarthritis studies, which demonstrated favourable effects on pain, imaging, and biomarkers following injectable PPS treatment.