Pentosan polysulfate

Pentosan polysulfate may be used either by mouth or in the bladder to treat interstitial cystitis/painful bladder syndrome (IC/PBS).[1] A older review found improvements in pain (36%), urgency (28%), and frequency (54%), but that it does not change the frequency of urination at night.[1][2] More recent trials, however, found it to be of no benefit.[1]

PPS has been studied in knee osteoarthritis, though evidence to support such use is poor as of 2003.[3] There is some theoretical evidence that it should help.[4]

PPS is being studied as a potential treatment of Creutzfeldt–Jakob disease (CJD). The rationale for this treatment was unclear but it was subsequently shown in prion-infected mouse neuroblastoma cells that PPS could rapidly reduce the levels of abnormal (scrapie) prion without affecting the normal cellular isoform.[8] As PPS can bind to the cellular isoform of the prion protein, it may stabilise this form and prevent its conversion to the pathological (scrapie) isoform.[9]

The treatment[10] of one patient in Northern Ireland and around six other patients in mainland Britain were reported in the press.[11] No patients showed signs of clinical improvement, however the disease was very advanced when the therapy was initiated.

Read et al. (1996) [12] used three different doses of sodium PPS to treat 40 geriatric dogs with well-established clinical signs of chronic OA with SC injection. The 3 mg/kg dose was the most effective. In a study conducted with 10 elderly dogs with osteoarthritis given calcium PPS (3 mg/kg intramuscularly) once weekly for four weeks, the improvement in symptoms (seen at 1, 2, 3 and 7 weeks after initiation of therapy) was found to correlate with plasma indices of fibrinolytic activity and lipid profiles.[13] In a study in dogs with OA secondary to cranial cruciate ligament (CCL) deficiency, although no differences were identified in either functional outcome or radiographic progression using the oral calcium PPS compared with placebo, there were significantly lower levels of proteoglycan breakdown products in the synovial fluid of the osteoarthritic joints.[14] The efficacy of subcutaneous sodium PPS (3 mg/kg) was tested in 40 dogs with cranial cruciate ligament (CCL) instability and found to hasten recovery, as measured by more rapidly improved ground reaction forces (GRF), over 48 weeks.[15]

There are few published reports describing the use of PPS for equine joint disease, however the drug is being used for this indication in Australia. When administered to racing Thoroughbreds with chronic osteoarthritis (2 to 3 mg/kg, intramuscularly, once weekly for 4 weeks, then as required), PPS treatment improved but did not eliminate clinical signs of joint disease.[16] Articular cartilage fibrillation was substantially reduced by similar NaPPS treatment intramuscularly in nine horse with experimentally-induced carpal osteoarthritis.[17] Despite limited published studies on the effect of PPS in horses, most surveyed owners and trainers in Australia found the intramuscular PPS treatment to be highly efficacious when used as a prophylactic prior to competition.[18]