Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice in<scp>A</scp>ustralia

Kramer, CM; Tsang, AS; Koenig, T; Jeffcott, L. B.; Dart, CM; Dart, AJ

doi:10.1111/avj.12266

Cited by 17 publications

(13 citation statements)

References 23 publications

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“…It also enhances proteoglycan synthesis, including the production of aggrecan and hyaluronan (49), and has been shown to be efficacious as both a treatment and a prophylactic (51). The results of this study demonstrate that RRV infection results in cartilage thinning by increasing the levels of ADAMTS-4 and ADMATS-5 (aggrecanase 1 and 2, respectively), which in turn disrupts the proteoglycan matrix in the cartilage, similar to the mechanism reported in osteoarthritis.…”

Section: Table 2 Long-term Pps Treatment Decreases the Expression Of supporting

confidence: 72%

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease

Herrero

Foo

Sheng

et al. 2015

J Virol

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Arthritogenic alphaviruses such as Ross River virus (RRV) and chikungunya virus (CHIKV) cause large-scale epidemics of severe musculoskeletal disease and have been progressively expanding their global distribution. Since its introduction in July 2014, CHIKV now circulates in the United States. The hallmark of alphavirus disease is crippling pain and inflammation of the joints, a similar immunopathology to rheumatoid arthritis. The use of glycans as novel therapeutics is an area of research that has increased in recent years. Here, we describe the promising therapeutic potential of the glycosaminoglycan (GAG)-like molecule pentosan polysulfate (PPS) to alleviate virus-induced arthritis. Mouse models of RRV and CHIKV disease were used to characterize the extent of cartilage damage in infection and investigate the potential of PPS to treat disease. This was assessed using histological analysis, real-time PCR, and fluorescence-activated cell sorting (FACS). Alphaviral infection resulted in cartilage destruction, the severity of which was alleviated by PPS therapy during RRV and CHIKV clinical disease. The reduction in cartilage damage corresponded with a significant reduction in immune infiltrates. Using multiplex bead arrays, PPS treatment was found to have significantly increased the anti-inflammatory cytokine interleukin-10 and reduced proinflammatory cytokines, typically correlated with disease severity. Furthermore, we reveal that the severe RRV-induced joint pathology, including thinning of articular cartilage and loss of proteoglycans in the cartilage matrix, was diminished with treatment. PPS is a promising new therapy for alphavirus-induced arthritis, acting to preserve the cartilage matrix, which is damaged during alphavirus infection. Overall, the data demonstrate the potential of glycotherapeutics as a new class of treatment for infectious arthritis. IMPORTANCEThe hallmark of alphavirus disease is crippling pain and joint arthritis, which often has an extended duration. In the past year, CHIKV has expanded into the Americas, with approximately 1 million cases reported to date, whereas RRV continues to circulate in the South Pacific. Currently, there is no licensed specific treatment for alphavirus disease, and the increasing spread of infection highlights an urgent need for therapeutic intervention strategies. Pentosan polysulfate (PPS) is a glycan derivative that is orally bioavailable, has few toxic side effects, and is currently licensed under the name Elmiron for the treatment of cystitis in the United States. Our findings show that RRV infection damages the articular cartilage, including a loss of proteoglycans within the joint. Furthermore, treatment with PPS reduced the severity of both RRV-and CHIKV-induced musculoskeletal disease, including a reduction in inflammation and joint swelling, suggesting that PPS is a promising candidate for drug repurposing for the treatment of alphavirus-induced arthritis.A rthropod-borne arthritogenic alphaviruses such as Ross River virus (RRV) and chikungu...

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Section: Table 2 Long-term Pps Treatment Decreases the Expression Of supporting

confidence: 72%

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease

Herrero

Foo

Sheng

et al. 2015

J Virol

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“…The profiles of the respondents approximated the distribution of Australian equine veterinarians described by Heath 13 and that reported in a recent survey of Australian equine veterinarians. 14 Respondents typically were experienced veterinarians (median year of graduation, 1999) and more often engaged in practices with a high proportion of horses in their case load (81-100%) or in practices where horses made up ≤ 50% of the practice. Very few respondents were in 50-80% equine practice.…”

Section: Discussionmentioning

confidence: 99%

Survey of equine castration techniques, preferences and outcomes among Australian veterinarians

et al. 2017

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“…A survey of members of the Equine Veterinarians Australia Special Interest Group provides some insight into how equine veterinarians administer pentosan polysulfate (PPS) and their perceptions of treatment efficacy for prevention and treatment of osteoarthritis (OA) when PPS is used alone or in combination with other drugs . A total of 76 vets (34.5%) completed the survey.…”

Section: Equinementioning

confidence: 99%

“…Interest Group provides some insight into how equine veterinarians administer pentosan polysulfate (PPS) and their perceptions of treatment efficacy for prevention and treatment of osteoarthritis (OA) when PPS is used alone or in combination with other drugs. 4 A total of 76 vets (34.5%) completed the survey. Respondents most commonly used PPS as a prophylactic agent prior to the horse competing (80.3%) than as treatment of OA, with 48.2% reporting that PPS prophylactic treatment was highly effective.…”

Section: A Survey Of Members Of the Equine Veterinarians Australia Spmentioning

confidence: 99%

In this issue – December 2014

Jackson¹,

Cabral²

2014

Aust Veterinary J

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Survey of the therapeutic approach and efficacy of pentosan polysulfate for the prevention and treatment of equine osteoarthritis in veterinary practice inAustralia

Abstract: All respondents used PPS for prophylaxis and/or treatment of OA despite limited published scientific evidence proving its efficacy in horses. Further research is necessary to provide evidence of the clinical efficacy of PPS for the prevention and treatment of OA in horses.

Cited by 17 publications

References 23 publications

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease

Pentosan Polysulfate: a Novel Glycosaminoglycan-Like Molecule for Effective Treatment of Alphavirus-Induced Cartilage Destruction and Inflammatory Disease

Survey of equine castration techniques, preferences and outcomes among Australian veterinarians

In this issue – December 2014

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