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Pentosan Polysulphate – The Ultimate Sugar

Dr HJ Marais. BVSc (Hons) MSc.

 Introduction 

Osteoarthritis (OA) is one of the most prevalent and debilitating diseases affecting horses, small animals and humans. Recently Pentosan polysulphate (PPS) has been recognised to act as a disease-modifying anti-arthritic agent and several in vivo studies have shown that PPS inhibits various processes that induce degeneration of articular cartilage. 

Mechanism of action 

Pentosan polysulfate is a heparin-like, semi-synthetic sulfated xylan heparinoid, derived from beech trees. It has been categorised as a disease-modifying anti-arthritic drug with anticoagulant, anti-inflammatory, fibrinolytic, and hypolipidemic properties. PPS has a smaller molecular weight than heparan sulfate (HS) or heparin and has many properties that mimic HS found on cell surface proteoglycans (PG) and in extracellular HS proteoglycans, which provide PPS with the ability to regulate physiological processes and equips it with various cell and tissue-protective properties. PPS has the ability to influence the overall health of the equine joint which led to it being classified as a structure-modifying osteoarthritic drug – these compounds treat the cause of the arthritis process rather than simply alleviate the pain produced by that process. 

PPS affects tissues and arthritic joints in several ways. It has no analgesic or primary pain-relieving effects in itself but acts as an HS mimetic to effect its beneficial effects in cartilage and has the ability to stimulate the biosynthesis of components of the extracellular matrix by limiting their degradation by its anticatabolic effects. PPS stimulates the synthesis of PG and increases the amount of these substances incorporated into the extracellular matrix.

Athletic use over time causes progressive OA with slow loss of PG from the cartilage matrix. The drug’s ability to replace these PGs is instrumental to its capacity to halt the progression of arthritis. PPS also stimulates synovial fibroblasts to produce increased amounts of high-molecular-weight hyaluronic acid. These actions improve the viscosity and volume of the joint fluid that lubricates and stabilises the joint and helps limit further degradation of cartilage. Additionally, PPS inhibits and modulates inflammatory mediators including histamine, serotonin, superoxide free radicals and proteins of the complement system, which have all been implicated in the degradation of the cartilage matrix. 

PPS has been shown to have additional effects on various other tissues, including the (a) promotion of repair of the degenerate intervertebral disc, (b) modulation of vascular coagulation, fibrinolysis and thrombocytopenia, (c) disruption of cell surface viral HS interactions, preventing host cell infection/viral replication, (d) anti-tumour agent in many cancer types, (e) tissue protective protease inhibitor, and (f) multifaceted exosite inhibitor of aggrecanases. In the OA joint, PPS (g) inhibits ADAMTS4 in chondrocytes and improves inhibitory properties of TIMP-3, (h) lipid removal from engorged subchondral blood vessels in OA joints, (i) inhibition of nerve growth factor production by osteocytes providing pain relief, (j) stimulation of hyaluronan synthesis by synoviocytes, fibroblasts and chondrocytes, and (k) modulates the differentiation and promotes the proliferation of bone-marrow-derived mesenchymal stem cells to progenitor cell lineages that have been employed in tissue repair strategies, in the degenerate intervertebral disc and osteoarthritic articular cartilage. 

Current, data clearly demonstrate the ability of PPS to stimulate the biosynthesis of components of the extracellular matrix accompanied by limiting their degradation by its anticatabolic effects. These beneficial pharmacological activities of PPS have resulted in its widespread use for the treatment of OA in both veterinary and human practice. Moreover, several studies confirm previous works demonstrating the ability of this drug to induce chondrogenic differentiation of mesenchymal progenitor stem cells in vivo and in vitro. 

Quality control 

Compounded veterinary drugs enjoy widespread use in clinical practice currently. Some concerns about their quality and consistency remain prevalent. A recent study (July 2024) performed in the USA evaluated the potency of commercially sourced PPS, obtained from six different compounding pharmacies. Their findings revealed significant variability in the actual potency of these products compared to their labelled concentrations. One product contained only 22% of the labelled PPS concentration, while others ranged from 52% to 92% of the labelled potency. Veterinarians, horse and dog owners should therefore prioritize using medications of which the final potency of the finished product is at least 90% of the labelled quantity of the active ingredient. By doing so, they can provide more effective and safer treatments for osteoarthritis, ultimately enhancing the well-being and performance of affected animals. The author has used PPS compounded by V-Tech South Africa in the past and has been satisfied with the clinical response. This compounding pharmacy is also able to provide assay results from each batch produced. 

Conclusion 

PPS acts by improving joint lubrication, reducing inflammation and bone bruising, and stimulating cartilage repair mechanisms—each a critical battlefield in the war against OA. In the ever-evolving landscape of osteoarthritis treatment, PPS is emerging as a management tool that has both positive structural and biochemical effects on the OA joint. 

References 

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