-
The Canadian Journal of Urology Dec 2023How should a conscientious physician advise patients with Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) when they want to know if taking Pentosan Polysulfate...
How should a conscientious physician advise patients with Interstitial Cystitis /Bladder Pain Syndrome (IC/BPS) when they want to know if taking Pentosan Polysulfate Sodium (PPS) will lead to loss of vision? Ever since the initial report from Pearce et al in 2018 suggesting that PPS usage can lead to the development of pigmented maculopathy (PM), my patients have been inundated with solicitations from attorneys looking to sign up clients for class action lawsuits.1 While there have been additional reports suggesting a relationship between PPS exposure and the development of PM, Ludwig et al found that there was no difference in the rate of macular disease between patients with documented IC/BPS who had taken PPS and those with IC/BPS with no history of PPS use.2 The large size of Ludwig's study certainly suggests that PPS may not cause PM to develop, and if the rate of PM in the IC population is higher than in controls, it may be due to the disease itself and not from the medication. In this manuscript, Proctor clearly describes the immune inflammatory response that is responsible for the development of the bladder damage seen with IC/BPS. Also, he describes how inflammatory mediators can enter the blood stream and might be a potential cause for the development of PM.3 This is a thought-provoking hypothesis that demands further evaluation. I have prescribed PPS since its approval and have many patients who feel it is an essential part of their IC treatment regimen. There is no other prescription medication that functions in the same fashion. I require them to follow the FDA recommendations for annual eye exams to look for PM development. I also advise patients that as they improve, we will discuss dose reduction and even discontinuation if their IC symptoms have abated. By following these suggestions, one should be able to continue to prescribe PPS for appropriate patients while carefully monitoring them for PM. I found this article extremely informative and will refer to it when counseling patients about IC/BPS and PPS.
Topics: Male; Humans; Pentosan Sulfuric Polyester; Cystitis, Interstitial; Macular Degeneration
PubMed: 38104331
DOI: No ID Found -
PloS One 2022Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that...
Hepcidin which is the crucial regulator of iron homeostasis, produced in the liver in response to anemia, hypoxia, or inflammation. Recent studies have suggested that hepcidin and iron metabolism are involved in osteoporosis by inhibiting osteoblast function and promoting osteoclastogenesis. Pentosan polysulfate (PPS) is a heparin analogue and promising novel therapeutic for osteoarthritis (OA). This study was undertaken to determine whether PPS inhibits hepcidin-facilitated osteoclast (OC) differentiation and iron overload. Canine (n = 3) bone marrow mononuclear cells were differentiated to OC by macrophage colony-stimulating factor and receptor-activator of nuclear factor kappaB ligand with the treatment of hepcidin1 (200, 400, 800, 1200 nmol/L) and PPS (1, 5, 10, 20, 40 μg/mL). Differentiation and function of OC were accessed using tartrate-resistant acid phosphate staining and bone resorption assay while monitoring ferroportin1 (FPN1) and iron concentration by immunocytochemistry. Gene expression of OC for cathepsin K (CTK), matrix metallopeptidase-9, nuclear factor of activated-T-cells cytoplasmic 1 and FPN1 was examined. Hepcidin1 showed significant enhancement of OC number at 800 nmol/L (p<0.01). PPS impeded hepcidin-facilitated OC at 1, 5 and 10 μg/mL and reduction of resorption pits at 5 and 10 μg/mL (p< 0.01). All OC specific genes were downregulated with PPS, specifically in significant manner with CTK at higher concentrations. However, heparin induced FPN1 internalization and degradation was inhibited at higher concentrations of PPS while restoring iron-releasing capability of OC. We demonstrate for the first time that PPS is a novel-inhibitor of hepcidin-facilitated OC formation/function which might be beneficial for treatment of OA and osteoporosis.
Topics: Animals; Bone Marrow; Bone Resorption; Cell Differentiation; Dogs; Heparin; Hepcidins; Iron; Osteoarthritis; Osteoclasts; Osteoporosis; Pentosan Sulfuric Polyester; RANK Ligand
PubMed: 35299233
DOI: 10.1371/journal.pone.0265596 -
Urology Jan 2021To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is...
OBJECTIVE
To conduct a review of current literature to assess whether an association exists between Pentosan Polysulfate Sodium and the development of macular disease, as it is the only oral medication approved by the Food and Drug Administration for the management of interstitial cystitis.
MATERIALS AND METHODS
A systematic review was conducted by the authors separately, with review methods established prior to the conduct of the review. Databases searched included PubMed, Ovid, Medline, EBSCO, and Google Scholar. A search was conducted for the terms "Pentosan Polysulfate Maculopathy," "Pentosan Polysulfate Retinopathy," and "Interstitial Cystitis Maculopathy." All papers reporting on primary data were included. There were no study sponsors.
RESULTS
A total of 14 papers reporting on primary data were identified. Most papers reported on the development of macular disease in the setting of chronic pentosan polysulfate sodium exposure. No randomized controlled trials have been performed to date and data was insufficient to perform a meta-analysis. Nevertheless, patients with interstitial cystitis were more likely to receive a diagnosis of maculopathy after several years of the medication use.
CONCLUSION
Although the nature of the published studies renders them prone to confounders, currently available data suggest an increased risk for developing maculopathy after years of pentosan polysulfate sodium use. In light of this, and the marginal effectiveness of the medication for the average individual, we suggest that education be provided as to the possible association and that regular ophthalmic evaluation be recommended for patients who are continued on chronic Pentosan Polysulfate Sodium.
Topics: Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Prevalence; Urologists
PubMed: 33045286
DOI: 10.1016/j.urology.2020.08.072 -
The Journal of Veterinary Medical... Oct 2022The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in...
The aim of this study was to investigate the anti-hepcidin effect of pentosan polysulfate (PPS) in Mongolian horses. Twenty-six healthy horses were randomly allocated in to two-groups; one group was treated with a PPS once a week for 4-weeks while another group keeping as placebo. Blood samples at day 0 (D0), before race (BR; day 28) and after race (AR; day 28) were analyzed for serum biochemistry, hepcidin and iron concentrations. Significant reduction of hepcidin was observed at AR in PPS group when compared with BR placebo (P<0.05) and AR placebo (P<0.01). Mean hepcidin concentration difference of D0-BR and BR-AR in PPS was greater than the placebo whereas the iron concentration difference is reduced compared to placebo. Results indicate a novel therapeutic application of PPS as an anti-hepcidin compound to control hepcidin in horses while emphasizing further molecular studies.
Topics: Animals; Horses; Iron; Pentosan Sulfuric Polyester
PubMed: 36047165
DOI: 10.1292/jvms.22-0113 -
The Analyst Aug 2019Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan,...
Pentosan polysulfate (PPS) is a semi-synthetic glycosaminoglycan (GAG) mimetic. PPS, synthesized through the chemical sulfonation of a plant-derived β-(1 → 4)-xylan, is the active pharmaceutical ingredient of the drug Elmiron™ used to treat interstitial cystitis. Unlike natural GAGs that can be enzymatically broken down into oligosaccharides for analysis, PPS is an unnatural polyanionic polysaccharide and is not amenable to such an analytical approach. Instead reactive oxygen species were used for the controlled depolymerization of PPS and the resulting oligosaccharide fragments were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to obtain bottom-up information on its composition. Because PPS has an average molecular weight ranging from 4000 to 6000 Da, similar to that of low molecular weight heparin, this suggested that it might be possible to use LC-MS on its intact chains and perform top-down analysis. The bottom-up and top-down analysis of PPS provides the first detailed compositional and structural information on PPS. Finally, we examined whether PPS would interfere with polysaccharide lyases and hydrolases, used in the analysis of natural GAGs such as chondroitin sulfates, heparan sulfate, and keratan sulfates. We found that PPS did not interfere with GAG analysis, suggesting that a combination of chemical and enzymatic treatment could be used to analyze samples containing both natural GAGs and PPS.
Topics: Chromatography, Liquid; Glycosaminoglycans; Hydrogen Peroxide; Mass Spectrometry; Oligosaccharides; Organometallic Compounds; Oxidation-Reduction; Pentosan Sulfuric Polyester
PubMed: 31287456
DOI: 10.1039/c9an01006h -
Fundamental & Clinical Pharmacology Oct 2022Pentosan polysulfate sodium (PPS) is a polysulfated glycosaminoglycan approved for the treatment of interstitial cystitis. It also showed renoprotective effects in...
Pentosan polysulfate sodium (PPS) is a polysulfated glycosaminoglycan approved for the treatment of interstitial cystitis. It also showed renoprotective effects in chronic kidney injury models, for example, 5/6 nephrectomy and diabetic nephropathy (DN). In the present study, we addressed to evaluate the therapeutic value of PPS in DN of rats in combination with losartan (LSR). Sixty male Sprague-Dawley rats were randomly divided into six groups: control group, untreated diabetic groups (8 and 16 weeks after diabetes induction by streptozotocin "STZ", 60 mg/kg, intraperitoneal [I.P.]), LSR-treated diabetic group (10 mg/kg/day, P.O.), PPS-treated diabetic group (25 mg/kg/day, P.O.), and combination-treated diabetic group. Drug treatment was started 8 weeks after induction of diabetes and continued for a further 8 weeks. Renal functions, albuminuria, renal IL-6, oxidative stress, and renal histopathology were evaluated. STZ-treated diabetic rats developed progressive albuminuria, renal dysfunction, and significant glomerular change 16 weeks after induction of diabetes. Administration of PPS, alone or in combination with LSR, showed some beneficial effects on DN evolution and significantly decreased renal inflammation as detected by IL-6 level. The best beneficial effect on DN evolution was obtained by PPS sole therapy based on albuminuria evaluation and renal histopathology. However, the combination of PPS and LSR did not show additive benefits. This study reported that the renoprotection of PPS in the setting of DN is evident by exerting anti-inflammatory and antioxidant effects, but this effect could be masked when combined with an angiotensin receptor blocker.
Topics: Albuminuria; Animals; Anti-Inflammatory Agents; Diabetes Mellitus, Experimental; Diabetic Nephropathies; Interleukin-6; Kidney; Losartan; Male; Pentosan Sulfuric Polyester; Rats; Rats, Sprague-Dawley; Streptozocin
PubMed: 35434832
DOI: 10.1111/fcp.12781 -
Expert Opinion on Pharmacotherapy Aug 2019
PubMed: 31070933
DOI: 10.1080/14656566.2019.1615056 -
Cold Spring Harbor Perspectives in... Mar 2017Although an effective therapy for prion disease has not yet been established, many advances have been made toward understanding its pathogenesis, which has facilitated... (Review)
Review
Although an effective therapy for prion disease has not yet been established, many advances have been made toward understanding its pathogenesis, which has facilitated research into therapeutics for the disease. Several compounds, including flupirtine, quinacrine, pentosan polysulfate, and doxycycline, have recently been used on a trial basis for patients with prion disease. Concomitantly, several lead antiprion compounds, including compound B (compB), IND series, and anle138b, have been discovered. However, clinical trials are still far from yielding significantly beneficial results, and the findings of lead compound studies in animals have highlighted new challenges. These efforts have highlighted areas that need improvement or further exploration to achieve more effective therapies. In this work, we review recent advances in prion-related therapeutic research and discuss basic scientific issues to be resolved for meaningful medical intervention of prion disease.
Topics: Aminopyridines; Animals; Creutzfeldt-Jakob Syndrome; Disease Models, Animal; Doxycycline; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Pentosan Sulfuric Polyester; Quinacrine; Randomized Controlled Trials as Topic; Translational Research, Biomedical
PubMed: 27836910
DOI: 10.1101/cshperspect.a024430 -
Scientific Reports May 2024In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate...
In this population-based cohort study, we investigated screening practices for maculopathy and incidences of specific macular/retinal conditions in pentosan polysulfate (PPS) users and assessed the relationship between these outcomes and drug exposure levels. Using a health claims database that covers approximately 50 million Koreans, we identified 138,593 individuals who were prescribed PPS between 2010 and 2021. For the 133,762 PPS users who initiated therapy between 2012 and 2021, the cumulative PPS dose for each participant was evaluated, and based on their cumulative PPS dose, patients were categorized into the high-risk (≥ 500 g), low-risk (50-500 g), and minimal exposure (< 50 g) groups. We analyzed the performance and methods of these examination methods used between 2018 and 2021 and compared them among cumulative dose groups to determine whether high-risk users underwent maculopathy screening more frequently or appropriately. We assessed the cumulative incidence of overall macular degeneration and maculopathy excluding common macular diseases following PPS therapy initiation. Most PPS users (99.7%) received a cumulative PPS dose < 500 g and the high- and low-risk groups comprised 445 (0.3%) and 22,185 (16.6%) patients, respectively. During the study period, monitoring examinations were conducted in 52.6% and 49.4% of high- and low-risk patients, respectively, revealing no significant difference between the two groups (P = 0.156). No significant differences were observed in the annual percentages of patients receiving ophthalmic examinations between the high- and low-risk groups (all P > 0.05). The cumulative incidences of overall macular degeneration and maculopathy excluding common macular diseases in high-risk users were 19.3% and 9.0%, respectively, which were significantly different from those of low-risk users (both P < 0.001). Multivariate Cox regression analysis revealed significantly higher risks of maculopathy excluding common macular diseases in the low- (Hazard ratio [HR] of 1.55 [95% CI 1.13-2.12]) and high-risk groups (HR of 1.66 [95% CI 1.22-2.27]) compared to the minimal exposure group. Our findings suggest a need for increased emphasis on PPS maculopathy screening in high-risk patients, highlighting raising awareness regarding exposure-dependent risks and the establishment of screening guidelines.
Topics: Humans; Pentosan Sulfuric Polyester; Male; Female; Middle Aged; Macular Degeneration; Risk Assessment; Aged; Adult; Incidence; Republic of Korea; Mass Screening; Cohort Studies
PubMed: 38760453
DOI: 10.1038/s41598-024-62041-y -
Investigative Ophthalmology & Visual... Nov 2020Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS...
PURPOSE
Individuals with pentosan polysulfate sodium (PPS) maculopathy commonly report symptoms of prolonged dark adaptation and difficulty reading. We hypothesize that PPS maculopathy causes degradation of visual function not fully captured with visual acuity testing.
METHODS
Subjects with PPS maculopathy underwent multimodal evaluation of retinal structure and function. Structural changes were graded as moderate or advanced. Patient-reported visual function was assessed with the National Eye Institute Visual Function Questionnaire 39 (NEI-VFQ-39) and Low Luminance Questionnaire (LLQ). Objective functional evaluations included Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA), Pelli-Robson contrast sensitivity, mesopic microperimetry, and dark adaptometry. Functional testing results were correlated with structural disease category.
RESULTS
Thirteen patients (26 eyes), median age 62 years (range, 37-76), completed the study. Median ETDRS letter score was 82 (Snellen equivalent 20/25). Median NEI-VFQ-39 and LLQ composite scores were 65 (range, 33-88) and 41 (range, 20-92), respectively. Median contrast sensitivity was 1.65 (range, 0.15-1.95), and median mesopic microperimetry average thresholds and percent reduced thresholds were 26 decibels (range, 0.4-28.6) and 21.6% (range, 0-100%), respectively. Median rod intercept time was 14.1 minutes (range, 4.4-20.0). Eyes with advanced disease based on retinal structure had significantly worse retinal function for several testing modalities.
CONCLUSIONS
PPS maculopathy causes considerable visual function degradation that is not fully captured with BCVA testing. There was good correlation between other measures of visual function and disease severity. These findings deepen our concern regarding this patient safety issue.
Topics: Adult; Aged; Anticoagulants; Contrast Sensitivity; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Sickness Impact Profile; Surveys and Questionnaires; Vision Disorders; Visual Acuity; Visual Field Tests; Visual Fields
PubMed: 33231621
DOI: 10.1167/iovs.61.13.33