-
CMAJ : Canadian Medical Association... May 2021
Topics: Anticoagulants; Cystitis, Interstitial; Humans; Macular Degeneration; Pentosan Sulfuric Polyester; Time Factors; Vision Disorders
PubMed: 33941523
DOI: 10.1503/cmaj.201900 -
ImmunoTargets and Therapy 2016Transmissible spongiform encephathalopathies or prion diseases are a group of neurological disorders characterized by neuronal loss, spongiform degeneration, and... (Review)
Review
Transmissible spongiform encephathalopathies or prion diseases are a group of neurological disorders characterized by neuronal loss, spongiform degeneration, and activation of astrocytes or microglia. These diseases affect humans and animals with an extremely high prevalence in some species such as deer and elk in North America. Although rare in humans, they result in a devastatingly swift neurological progression with dementia and ataxia. Patients usually die within a year of diagnosis. Prion diseases are familial, sporadic, iatrogenic, or transmissible. Human prion diseases include Kuru, sporadic, iatrogenic, and familial forms of Creutzfeldt-Jakob disease, variant Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, and fatal familial insomnia. The causative agent is a misfolded version of the physiological prion protein called PrP(Sc) in the brain. There are a number of therapeutic options currently under investigation. A number of small molecules have had some success in delaying disease progression in animal models and mixed results in clinical trials, including pentosan polysulfate, quinacrine, and amphotericin B. More promisingly, immunotherapy has reported success in vitro and in vivo in animal studies and clinical trials. The three main branches of immunotherapy research are focus on antibody vaccines, dendritic cell vaccines, and adoptive transfer of physiological prion protein-specific CD4(+) T-lymphocytes. Vaccines utilizing antibodies generally target disease-specific epitopes that are only exposed in the misfolded PrP(Sc) conformation. Vaccines utilizing antigen-loaded dendritic cell have the ability to bypass immune tolerance and prime CD4(+) cells to initiate an immune response. Adoptive transfer of CD4(+) T-cells is another promising target as this cell type can orchestrate the adaptive immune response. Although more research into mechanisms and safety is required, these immunotherapies offer novel therapeutic targets for prion diseases.
PubMed: 27529062
DOI: 10.2147/ITT.S64795 -
BMJ Open May 2024Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain...
INTRODUCTION
Knee osteoarthritis (OA) is the most prevalent arthritis type and a leading cause of chronic mobility disability. While pain medications provide only symptomatic pain relief; growing evidence suggests pentosan polysulfate sodium (PPS) is chondroprotective and could have anti-inflammatory effects in knee OA. This study aims to explore the efficacy and safety of oral PPS in symptomatic knee OA with dyslipidaemia.
METHODS AND ANALYSIS
MaRVeL is a phase II, single-centre, parallel, superiority trial which will be conducted at Royal North Shore Hospital, Sydney, Australia. 92 participants (46 per arm) aged 40 and over with painful knee OA and mild to moderate structural change on X-ray (Kellgren and Lawrence grade 2 or 3) will be recruited from the community and randomly allocated to receive two cycles of either oral PPS or placebo for 5 weeks starting at baseline and week 11. Primary outcome will be the 16-week change in overall average knee pain severity measured using an 11-point Numeric Rating Scale. Main secondary outcomes include change in knee pain, patient global assessment, physical function, quality of life and other structural changes. A biostatistician blinded to allocation groups will perform the statistical analysis according to the intention-to-treat principle.
ETHICS AND DISSEMINATION
The protocol has been approved by the NSLHD Human Research Ethics Committee (HREC) (2021/ETH00315). All participants will provide written informed consent online. Study results will be disseminated through conferences, social media and academic publications.
TRIAL REGISTRATION NUMBERS
Australian New Zealand Clinical Trial Registry (ACTRN12621000654853); U1111-1265-3750.
Topics: Humans; Osteoarthritis, Knee; Pentosan Sulfuric Polyester; Dyslipidemias; Quality of Life; Male; Treatment Outcome; Female; Middle Aged; Clinical Trials, Phase II as Topic; Australia; Pain Measurement; Adult
PubMed: 38777590
DOI: 10.1136/bmjopen-2023-083046 -
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 -
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 -
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 -
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 -
Retina (Philadelphia, Pa.) Jul 2021To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis.
PURPOSE
To investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis.
METHODS
A 27-item online survey was distributed to an international mailing list of individuals with interstitial cystitis in November 2018. Demographic characteristics, PPS exposure history, subjective visual function, and previous macular diagnoses were queried. The impact of PPS use, grouped by tertile of cumulative exposure, on visual function and macular diagnoses was assessed with multivariate logistic regression.
RESULTS
The survey was completed by 912 respondents. Eight hundred and sixty-one (96.4%) were women, and the median age was 55 [interquartile range (IQR), 45-64 years]. Among PPS users, the median exposure was 547.5 g (IQR, 219-1,314 g). Respondents in the highest PPS exposure tertile were more likely to report difficulty with reading small print [adjusted odds ratio 2.29, 95% confidence interval (CI) 1.15-4.57] and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted odds ratio 2.41, 95% CI 1.44-4.03) than unexposed respondents.
CONCLUSION
In this large sample of individuals with interstitial cystitis, those in the highest PPS exposure category were more likely to have difficulties reading small print and to report a previous diagnosis of macular disease. Further study of objective measures of visual function in PPS users is warranted.
Topics: Anticoagulants; Cystitis, Interstitial; Female; Follow-Up Studies; Humans; Male; Middle Aged; Pentosan Sulfuric Polyester; Retinal Diseases; Retinal Pigment Epithelium; Retrospective Studies; Surveys and Questionnaires
PubMed: 33332810
DOI: 10.1097/IAE.0000000000003078 -
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 -
Veterinary Sciences Apr 2024Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair... (Review)
Review
Musculoskeletal injuries such as equine osteoarthritis, osteoarticular defects, tendonitis/desmitis, and muscular disorders are prevalent among sport horses, with a fair prognosis for returning to exercise or previous performance levels. The field of equine medicine has witnessed rapid and fruitful development, resulting in a diverse range of therapeutic options for musculoskeletal problems. Staying abreast of these advancements can be challenging, prompting the need for a comprehensive review of commonly used and recent treatments. The aim is to compile current therapeutic options for managing these injuries, spanning from simple to complex physiotherapy techniques, conservative treatments including steroidal and non-steroidal anti-inflammatory drugs, hyaluronic acid, polysulfated glycosaminoglycans, pentosan polysulfate, and polyacrylamides, to promising regenerative therapies such as hemoderivatives and stem cell-based therapies. Each therapeutic modality is scrutinized for its benefits, limitations, and potential synergistic actions to facilitate their most effective application for the intended healing/regeneration of the injured tissue/organ and subsequent patient recovery. While stem cell-based therapies have emerged as particularly promising for equine musculoskeletal injuries, a multidisciplinary approach is underscored throughout the discussion, emphasizing the importance of considering various therapeutic modalities in tandem.
PubMed: 38787162
DOI: 10.3390/vetsci11050190