Effects of intra‐articular sodium pentosan polysulfate and glucosamine on the cytology, total protein concentration and viscosity of synovial fluid in horses

Kwan, C; Bell, Robin J.; Koenig, T; Bischofberger, Andrea S; Horadagoda, N. U.; Perkins, N. R.; Jeffcott, L. B.; Dart, AJ

doi:10.1111/j.1751-0813.2012.00959.x

Cited by 18 publications

(19 citation statements)

References 30 publications

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“…The drug also has been used extensively in animals to treat OA [13], [16], [30], and is available commercially for OA veterinary use. The molecular mechanisms leading to the improvement in cartilage disease are not entirely clear, although PPS has been shown to repress MMP expression and inflammation, as well as NF-kB activation.…”

Section: Discussionmentioning

confidence: 99%

“…It also has been shown to promote chondrogenesis in animals with osteoarthritis (OA) [11]–[13], and has been used off-label to treat OA patients [14]–[15]. Sodium or calcium salts of PPS are effective at reducing joint inflammation, promoting fibrinolysis, stimulating hyaluronan synthesis by synovial fibroblasts, and stimulating proteoglycan synthesis by chondrocytes [16]–[17]. They also promote proliferation and chondrogenic differentiation of adult human bone marrow mesenchymal stem cells [18].…”

Section: Introductionmentioning

confidence: 99%

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Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses

Schuchman

Lai

et al. 2013

PLoS ONE

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BackgroundPentosan polysulfate (PPS) is an FDA-approved, oral medication with anti-inflammatory and pro-chondrogenic properties. We have previously shown that animal models of the mucopolysaccharidoses (MPS) exhibit significant inflammatory disease, contributing to cartilage degeneration. Enzyme replacement therapy (ERT) only partly reduced inflammation, and anti-TNF-alpha antibody therapy significantly enhanced clinical and pathological outcomes. Here we describe the use of PPS for the treatment of MPS type VI rats.Methodology/Principal FindingsTreatment began during prenatal development and at 1 and 6 months of age. All animals were treated until they were 9 months old. Significant reductions in the serum and tissue levels of several inflammatory markers (e.g., TNF-alpha, MIP-1alpha and RANTES/CCL5) were observed, as was reduced expression of inflammatory markers in cultured articular chondrocytes. ADAMTS-5/aggrecanase-2 levels also were reduced in chondrocytes, consistent with an elevation of serum tissue inhibitor of metalloproteinase 1. Marked improvements in motility and grooming behavior occurred, along with a reduction in eye and nasal secretions and a lessening of the tracheal deformities. MicroCT and radiographic analyses further revealed that the treated MPS skulls were longer and thinner, and that the teeth malocclusions, misalignments and mineral densities were improved. MicroCT analysis of the femurs and vertebrae revealed improvements in trabecular bone mineral densities, number and spacing in a subset of treated MPS animals. Biomechanical assessments of PPS-treated spines showed partially restored torsional behaviors, suggesting increased spinal stability. No improvements were observed in cortical bone or femur length. The positive changes in the PPS-treated MPS VI rats occurred despite glycosaminoglycan accumulation in their tissues.ConclusionsBased on these findings we conclude that PPS could be a simple and effective therapy for MPS that might provide significant clinical benefits alone and in combination with other therapies.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses

Schuchman

Lai

et al. 2013

PLoS ONE

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“…Joint disease is widespread in horses and encompasses a spectrum of pathologies, ranging from relatively minor insults (e.g., synovitis, small osteochondral lesions) to more debilitating conditions (e.g., intra‐articular fractures, severe osteoarthritis) . Over the past 20 years, corticosteroids and hyaluronic acid have been the mainstays of intra‐articular medication in horses; the intra‐articular use of pentosan polysulfate has also been recently reported . All of these treatments are intended to achieve anti‐inflammatory and chondroprotective effects, thereby mitigating the impact of traumatic and inflammatory arthritides.…”

Section: Discussionmentioning

confidence: 99%

Intra‐Articular Use of a Platelet‐Rich Product in Normal Horses: Clinical Signs and Cytologic Responses

Textor

Tablin

2013

Veterinary Surgery

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“…Subsequent work identified the anti-inflammatory properties of PPS, leading to its use as an oral treatment for interstitial cystitis (IC, painful bladder syndrome; Elmiron) [18], [19]. Injectable PPS forms also are used to treat osteoarthritis in veterinary medicine (e.g., Cartophen Vet) [20], [21]. The bioavailability of the injectable form is greater than oral [personal communication – bene pharmaChem, Germany], with the majority of the drug targeted to the liver and kidney.…”

Section: Introductionmentioning

confidence: 99%

Dose Responsive Effects of Subcutaneous Pentosan Polysulfate Injection in Mucopolysaccharidosis Type VI Rats and Comparison to Oral Treatment

Frohbergh

Meng

et al. 2014

PLoS ONE

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BackgroundWe previously demonstrated the benefits of daily, oral pentosan polysulfate (PPS) treatment in a rat model of mucopolysaccharidosis (MPS) type VI. Herein we compare these effects to once weekly, subcutaneous (sc) injection. The bioavailability of injected PPS is greater than oral, suggesting better delivery to difficult tissues such as bone and cartilage. Injected PPS also effectively treats osteoarthritis in animals, and has shown success in osteoarthritis patients.Methodology/Principal FindingsOne-month-old MPS VI rats were given once weekly sc injections of PPS (1, 2 and 4 mg/kg, human equivalent dose (HED)), or daily oral PPS (4 mg/kg HED) for 6 months. Serum inflammatory markers and total glycosaminoglycans (GAGs) were measured, as were several histological, morphological and functional endpoints. Overall, weekly sc PPS injections led to similar or greater therapeutic effects as daily oral administration. Common findings between the two treatment approaches included reduced serum inflammatory markers, improved dentition and skull lengths, reduced tracheal deformities, and improved mobility. Enhanced effects of sc treatment included GAG reduction in urine and tissues, greater endurance on a rotarod, and better improvements in articular cartilage and bone in some dose groups. Optimal therapeutic effects were observed at 2 mg/kg, sc. No drug-related increases in liver enzymes, coagulation factor abnormalities or other adverse effects were identified following 6 months of sc PPS administration.ConclusionsOnce weekly sc administration of PPS in MPS VI rats led to equal or better therapeutic effects than daily oral administration, including a surprising reduction in urine and tissue GAGs. No adverse effects from sc PPS administration were observed over the 6-month study period.

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Effects of intra‐articular sodium pentosan polysulfate and glucosamine on the cytology, total protein concentration and viscosity of synovial fluid in horses

Abstract: Intra-articular administration of combined pentosan polysulfate and glucosamine causes a mild inflammatory synovitis that is not substantially different to that elicited by injection of a similar volume of saline and so we conclude that these drugs are safe to use in the horse.

Cited by 18 publications

References 30 publications

Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses

Pentosan Polysulfate: A Novel Therapy for the Mucopolysaccharidoses

Intra‐Articular Use of a Platelet‐Rich Product in Normal Horses: Clinical Signs and Cytologic Responses

Dose Responsive Effects of Subcutaneous Pentosan Polysulfate Injection in Mucopolysaccharidosis Type VI Rats and Comparison to Oral Treatment

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