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Journal of Inherited Metabolic Disease Mar 2024Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function....
Open-label, single-center, clinical study evaluating the safety, tolerability and clinical effects of pentosan polysulfate sodium in subjects with mucopolysaccharidosis I.
Lysosomal enzyme deficiency in mucopolysaccharidosis (MPS) I results in glycosaminoglycan (GAG) accumulation leading to pain and limited physical function. Disease-modifying treatments for MPS I, enzyme replacement, and hematopoietic stem cell therapy (HSCT), do not completely resolve MPS I symptoms, particularly skeletal manifestations. The GAG reduction, anti-inflammatory, analgesic, and tissue remodeling properties of pentosan polysulfate sodium (PPS) may provide disease-modifying treatment for musculoskeletal symptoms and joint inflammation in MPS I following ERT and/or HSCT. The safety and efficacy of PPS were evaluated in four subjects with MPS I aged 14-19 years, previously treated with ERT and/or HSCT. Subjects received doses of 0.75 mg/kg or 1.5 mg/kg PPS via subcutaneous injections weekly for 12 weeks, then every 2 weeks for up to 72 weeks. PPS was well tolerated at both doses with no serious adverse events. MPS I GAG fragment (UA-HNAc [1S]) levels decreased at 73 weeks. Cartilage degradation biomarkers serum C-telopeptide of crosslinked collagen (CTX) type I (CTX-I) and type II (CTX-II) and urine CTX-II decreased in all subjects through 73 weeks. PROMIS scores for pain interference, pain behavior, and fatigue decreased in all subjects through 73 weeks. Physical function, measured by walking distance and dominant hand function, improved at 49 and 73 weeks. Decreased GAG fragments and cartilage degradation biomarkers, and positive PROMIS outcomes support continued study of PPS as a potential disease-modifying treatment for MPS I with improved pain and function outcomes.
Topics: Humans; Biomarkers; Cartilage; Enzyme Replacement Therapy; Mucopolysaccharidosis I; Pain; Pentosan Sulfuric Polyester; Adolescent; Young Adult
PubMed: 38467596
DOI: 10.1002/jimd.12715 -
Viruses Feb 2024Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are...
Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic virus with high contagion and mortality rates. Heparan sulfate proteoglycans (HSPGs) are ubiquitously expressed on the surface of mammalian cells. Owing to its high negatively charged property, heparan sulfate (HS) on the surface of host cells is used by many viruses as cofactor to facilitate viral attachment and initiate cellular entry. Therefore, inhibition of the interaction between viruses and HS could be a promising target to inhibit viral infection. In the current study, the interaction between the receptor-binding domain (RBD) of MERS-CoV and heparin was exploited to assess the inhibitory activity of various sulfated glycans such as glycosaminoglycans, marine-sourced glycans (sulfated fucans, fucosylated chondroitin sulfates, fucoidans, and rhamnan sulfate), pentosan polysulfate, and mucopolysaccharide using Surface Plasmon Resonance. We believe this study provides valuable insights for the development of sulfated glycan-based inhibitors as potential antiviral agents.
Topics: Animals; Heparin; Middle East Respiratory Syndrome Coronavirus; Sulfates; Glycosaminoglycans; Heparitin Sulfate; Mammals
PubMed: 38400013
DOI: 10.3390/v16020237 -
Investigative Ophthalmology & Visual... Feb 2024There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated...
PURPOSE
There are numerous reports of a distinctive maculopathy in adults exposed to pentosan polysulfate sodium (PPS), a drug prescribed to treat bladder discomfort associated with interstitial cystitis. We tested whether PPS treatment of mice injures RPE or retina to provide insight into the etiology of the human condition.
METHODS
Mice were fed PPS-supplemented chow over 14 months. RPE and retinal function was assessed by electroretinography (ERG) regularly. Following euthanasia, one eye was used for sagittal sectioning and histology, the contralateral for RPE flatmounting. ZO-1 positive RPE cell borders were imaged using confocal microscopy and cell morphology was analyzed using CellProfiler.
RESULTS
After 10 months of PPS treatment, we observed diminution of mean scotopic c-wave amplitudes. By 11 months, we additionally observed diminutions of mean scotopic a- and b-wave amplitudes. Analysis of flatmounts revealed altered RPE cell morphology and morphometrics in PPS-treated mice, including increased mean en face cell area and geometric eccentricity, decreased RPE cell solidity and extent, and cytosolic translocation of alpha-catenin, all markers of RPE cell stress. Sex and regional differences were seen in RPE flatmount measures. Shortened photoreceptor outer segments were also observed.
CONCLUSIONS
PPS treatment reduced RPE and later retina function as measured by ERG, consistent with a primary RPE injury. Post-mortem analysis revealed extensive RPE pleomorphism and polymegathism and modest photoreceptor changes. We conclude that PPS treatment of mice causes slowly progressing RPE and photoreceptor damage and thus may provide a useful model for some retinal pathologies.
Topics: Adult; Humans; Animals; Mice; Pentosan Sulfuric Polyester; Retina; Electroretinography; Causality; Retinal Diseases
PubMed: 38381414
DOI: 10.1167/iovs.65.2.28 -
Zhonghua Wai Ke Za Zhi [Chinese Journal... Feb 2024In 2022, American Urological Association updated the guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). A significant...
In 2022, American Urological Association updated the guideline for the diagnosis and treatment of interstitial cystitis/bladder pain syndrome (IC/BPS). A significant change has been made in treatment recommendations. The updated guideline no longer divided treatments into first-line through sixth-line tiers. Instead, treatment is categorized into behavioral/non-pharmacologic, oral medicines, bladder instillations, procedures, and major surgery. This change emphasizes the heterogeneity of IC/BPS patients and the importance of individualized treatment, overturns traditional unreasonable ideas about hierarchical and progressive treatment, and encourages patients and physicians to make treatment decisions together. At the same time, the panel emphasized the importance of early implementation of cystoscopy in patients suspected of Hunner lesions and warned against the possibility of pentosan polysulfate causing a unique retinal pigmentary maculopathy. Urinary reconstruction surgery was considered to only be used as a last resort for the treatment of IC/BPS, and there is uncertainty about the overall balance between benefits and risks/burdens. The updated guideline provides a new understanding and decision-making basis for the diagnosis and treatment of IC/BPS. However, it should be noted that the clinical characteristics of Chinese patients should be considered in practice and the application of the guideline should be localized.
Topics: Humans; Cystitis, Interstitial; Cystoscopy; Pentosan Sulfuric Polyester
PubMed: 38310379
DOI: 10.3760/cma.j.cn112139-20230713-00006 -
Current Opinion in Urology Mar 2024Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new... (Review)
Review
PURPOSE OF REVIEW
Despite available treatments, many bladder pain syndrome/interstitial cystitis (BPS/IC) patients continue to have poor quality of life. Thus, there is an urge for new therapies. Our manuscript aims to review papers about BPS/IC treatments published in the last 2 years.
RECENT FINDINGS
During this period, several treatments were tested, most of them new and others combining treatments already used. Pentosan polysulfate, interleukin 1 antagonist, low energy shock wave, physical therapy, hypnosis, acupuncture, clorpactin, dimethyl sulfoxide and hyaluronic acid plus botulinum toxin-A showed positive results. ASP3652 and lidocaine-releasing intravesical systems failed to prove their efficacy.
SUMMARY
Validation of these studies is arduous due to the broad spectre of BPS/IC phenotypes, small number of patients enrolled, distinct outcome measures and short-term follow-up. It is also important to highlight that some authors combined therapies, and others split central and peripheric phenotypes before treatment. Therefore, soon, phenotyping and combining therapies with a step-by-step approach will be needed in BPS/IC treatment.
Topics: Humans; Cystitis, Interstitial; Quality of Life; Administration, Intravesical; Botulinum Toxins, Type A; Lidocaine
PubMed: 38168016
DOI: 10.1097/MOU.0000000000001159 -
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 -
The Canadian Journal of Urology Dec 2023Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved... (Review)
Review
INTRODUCTION
Interstitial cystitis (IC) is a chronic disease with urinary tract symptoms and pain. Pentosan polysulfate (PPS) is the only U.S. Food and Drug Administration approved oral medication for the treatment of IC pain and symptoms. Recently, articles described a pigmentary maculopathy in IC patients on long term PPS therapy. Currently, there is no definitive study directly linking PPS as the cause of the pigmentary maculopathy. The aim of this review is to evaluate if PPS is the causative factor of the pigmentary maculopathy or if PPS use is only associated with the pigmentary maculopathy.
MATERIALS AND METHODS
A comprehensive review of peer reviewed journals using the search terms IC, maculopathy, mast cells, immune inflammatory components, Tamm-Horsfall protein, cations and tight junctions was performed to examine the pathophysiology and role of chronic inflammation in IC and known retinal maculopathies.
RESULTS
Chronic inflammatory cells have been reported in age-related macular degeneration choroid blood vessels and in bladder submucosal and detrusor layers in IC patients. Studies in IC and maculopathies demonstrate a significant milieu of activated chronic inflammatory and immunologic responses that cause a more "leaky" epithelium and a subsequent cascade of inflammatory events that results in the pathological changes seen in these two conditions.
CONCLUSIONS
After an analysis of the literature describing a pigmentary maculopathy in IC patients on long term PPS, a causal relationship does not appear to be present. An alternate model is proposed postulating that the causative factor for the pigmentary maculopathy is the underlying inflammatory state associated with IC and not PPS use.
Topics: Humans; Pentosan Sulfuric Polyester; Macular Degeneration; Cystitis, Interstitial; Pain; Inflammation
PubMed: 38104330
DOI: No ID Found -
Bladder (San Francisco, Calif.) 2023Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization....
OBJECTIVES
Pentosan Polysulfate (PPS) is the only oral treatment for interstitial cystitis (IC)-bladder pain syndrome (BPS) approved by the World Health Organization. Self-evaluation scales can provide more objective results on pre- and post-treatment satisfaction. The aim of this study was to investigate the effect of pentosan polysulfate treatment on symptoms in IC-BPS patients.
METHODS
This study included 37 adult male and female patients with IC-BPS who reported pain, urinary urgency, polyurea, and nocturia without urinary tract infection for a minimum of six months prior to the study and were taking 300 mg/day oral pentosan polysulfate. Pre- and post-treatment symptoms, Interstitial Cystitis Symptom Index (ICSI) Scores, quality of life (QoL) scores (1-4), and satisfaction conditions were examined.
RESULTS
Following the application of inclusion and exclusion criteria, mean age of 37 suitable patients was 46.0±11.9 years and 27% (10 individuals) of the patients were male. Pre-treatment, ICSI scores, and measures of satisfaction degree and QoL increased significantly after the treatment (p<0.001). Adverse reaction was detected in two patients (5.4%) among the patients treated with pentosan polysulfate.
CONCLUSIONS
Oral pentosan polysulfate for the treatment of interstitial cystitis/bladder pain syndrome treatment could achieve recovery in symptoms, increase Interstitial Cystitis Symptom Index score and improve quality of life and patient satisfaction.
PubMed: 37936582
DOI: 10.14440/bladder.2023.866 -
Ophthalmology. Retina Mar 2024To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
OBJECTIVE
To investigate the nationwide use of pentosan polysulfate (PPS) and screening practices for PPS maculopathy (PPM), with a focus on the timing and modalities used.
DESIGN
Population-based cohort study.
PARTICIPANTS
For evaluation of nationwide usage, 133 762 individuals who received PPS prescriptions between 2012 and 2021 were included. To investigate practice patterns, 55 487 individuals (referred to as overall users) who initiated PPS therapy between 2018 and 2020 were identified using the Health Insurance Review and Assessment database. After excluding patients with ophthalmic diseases before PPS administration, 34 857 PPS users without prior ophthalmic diseases were identified.
METHODS
Ophthalmic examinations performed after initiating PPS therapy were categorized as baseline and subsequent monitoring examinations. The timing and modalities employed for these examinations were analyzed. The annual trends in PPS utilization and maculopathy screening were evaluated by assessing the number of PPS users and determining the proportion of patients receiving retinal/macular examinations among these users.
MAIN OUTCOME MEASURES
Performance of baseline and subsequent monitoring examinations and timing and modalities used for screening.
RESULTS
The number of PPS users dramatically increased annually over the study period from 5494 in 2012 to 40 451 in 2021. However, the majority of PPS users did not undergo baseline or subsequent monitoring examinations for PPM. Only 27.2% and 12.4% of PPS users without prior ophthalmic disease underwent baseline and monitoring examinations, respectively. Funduscopy/fundus photography was the most commonly utilized, whereas OCT and fundus autofluorescence (FAF) were performed in only 45.2% and 5.3% of the PPS users without prior ophthalmic diseases for monitoring, respectively. The performance of the screening examinations differed significantly across the 3 different daily dose and duration groups (all P < 0.05).
CONCLUSIONS
This study highlights the lack of performance of baseline and monitoring examinations for maculopathy in most patients taking PPS in South Korea. The limited use of OCT and FAF suggests potential insensitivity in detecting PPM. These findings emphasize the need for improvements in screening practices, including increased awareness and referrals to ophthalmologists, utilization of more sensitive modalities, and regular monitoring to enable early detection of PPM.
FINANCIAL DISCLOSURE(S)
The authors have no proprietary or commercial interest in any materials discussed in this article.
Topics: Humans; Pentosan Sulfuric Polyester; Cohort Studies; Retinal Diseases; Macular Degeneration; Republic of Korea
PubMed: 37832716
DOI: 10.1016/j.oret.2023.10.005