SuperGAG biopolymers for treatment of excessive bladder permeability

Towner, Rheal A.; Meerveld, Beverley Greenwood‐Van; Mohammadi, Ehsan; Saunders, Debra; Smith, Nataliya; Sant, Grannum R.; Shain, Harrison C.; Jozefiak, Thomas H.; Hurst, Robert E.

doi:10.1002/prp2.709

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…Greenwood-Van Meerveld et al reported on restored bladder function and reduced bladder permeability by intravesical instillation of recombinant human proteoglycan 4 (lubricin, rhPRG4), a highly hydrophilic glycoprotein with anti-inflammatory properties in PS-induced IC in female SD rats [ 41 ]. The same research group also tested a novel high-molecular-weight GAG biopolymer (“SuperGAG”) that was more effective in restoring bladder function and relieving pain compared to CS [ 42 ]. Another emerging class of therapeutic GAGs involves semi-synthetic GAG-ethers (SAGE) offering both mucosal restoration and potent analgesic and anti-inflammatory effects.…”

Section: Resultsmentioning

confidence: 99%

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

et al. 2021

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Interstitial cystitis/bladder pain syndrome (IC/BPS) is a multifactorial, chronic bladder disorder with limited therapeutic options currently available. The present review provides an extensive overview of therapeutic approaches used in in vitro, ex vivo, and in vivo experimental models of IC/BPS. Publications were identified by electronic search of three online databases. Data were extracted for study design, type of treatment, main findings, and outcome, as well as for methodological quality and the reporting of measures to avoid bias. A total of 100 full-text articles were included. The majority of identified articles evaluated therapeutic agents currently recommended to treat IC/BPS by the American Urological Association guidelines (21%) and therapeutic agents currently approved to treat other diseases (11%). More recently published articles assessed therapeutic approaches using stem cells (11%) and plant-derived agents (10%), while novel potential drug targets identified were proteinase-activated (6%) and purinergic (4%) receptors, transient receptor potential channels (3%), microRNAs (2%), and activation of the cannabinoid system (7%). Our results show that the reported methodological quality of animal studies could be substantially improved, and measures to avoid bias should be more consistently reported in order to increase the value of preclinical research in IC/BPS for potential translation to a clinical setting.

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Section: Resultsmentioning

confidence: 99%

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

et al. 2021

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“…Recently, there have been studies dedicated to enhancing the effect of hyaluronic acid and chondroitin sulfate on bladder impermeability, in which “SuperGAGs” were developed as crosslinked GAG molecules with higher molecular weights. For both chondroitin sulfate and hyaluronic acid, these SuperGAGs have demonstrated greater effectiveness in restoring barrier function, characterized by impermeability, compared to regular GAGs [24 ▪ ,25].…”

Section: Discussionmentioning

confidence: 99%

Restoring the barrier of chronically damaged urothelium using chondroitin sulfate glycosaminoglycan-replenishment therapy

Rozenberg,

van Ginkel,

Janssen

2023

Current Opinion in Urology

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Purpose of review This study aims to further understand the physiological mechanism of chondroitin sulfate treatment on the urinary bladder in cases of inflammation, by investigating the effect of chondroitin sulfate therapy on recovery of urothelial barrier in an in-vitro chronic injury model. Recent findings With inflammatory bladder conditions, the urothelial barrier seems decreased. Glycosaminoglycan (GAG) replacement therapy is supposed to help restore this barrier. Clinical studies on inflammatory bladder conditions are complicated because of the heterogeneous patient population, hence the need for preclinical models. Summary In a model using porcine urothelial cells, functional barrier (TEER) and barrier markers were assessed. Chronic urothelial damage was simulated through protamine sulfate instillations with and without subsequent chondroitin sulfate instillations during 3 days. Chondroitin sulfate instillations significantly improved TEER compared to protamine sulfate treatment only (TEER difference 310 Ω.cm2, P < 0.001). This consistent effect over 3 days resulted in a significant higher mean TEER value in the chondroitin sulfate treated group (difference 1855 Ω.cm2, P < 0.001). Enhanced recovery of chondroitin sulfate and other barrier markers was observed. Chondroitin sulfate therapy shows promise in facilitating the recovery of the urothelial barrier in cases of chronic damage. This preclinical study lends support to the use of clinical GAG replenishment therapy for patients with a chronically impaired urothelium.

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“…SuperGAGs forms a 3-dimensional structure, adhering tightly to the bladder surface and creating a thicker bound water layer. Studies demonstrated that they are more effective in restoring impermeability compared to normal GAGs [ 46 , 47 ].…”

Section: Therapeutic Correction Of Barrier Dysfunctionmentioning

confidence: 99%

The urothelial barrier in interstitial cystitis/bladder pain syndrome: its form and function, an overview of preclinical models

van Ginkel,

Hurst,

Janssen

2023

Current Opinion in Urology

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Purpose of review Investigating bladder pain syndrome/interstitial cystitis (IC/BPS) preclinically is challenging. Various research models have been used to mimic the urothelial barrier closely and replicate the disease. The aim of this review is to discuss preclinical research related to the urothelial barrier in context of IC/BPS. Recent findings In vivo models mimic IC/BPS mainly with toxic substances in the urine, with protaminesulfate and proteoglycan deglycolysation resembling a temporary impaired barrier as seen in IC/BPS. This temporary increased permeability has also been found in vitro models. Glycosaminoglycan replenishment therapy has been described, in vivo and in vitro, to protect and enhance recover properties of the urothelium. The roles of immune and neurogenic factors in the pathogenesis of IC/BPS remains relatively understudied. Summary Preclinical studies provide opportunities to identify the involvement of specific pathologic pathways in IC/BPS. For further research is warranted to elucidate the primary or secondary role of permeability, together with inflammatory and neurogenic causes of the disease.

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SuperGAG biopolymers for treatment of excessive bladder permeability

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 6 publications

References 48 publications

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

A Systematic Review of Therapeutic Approaches Used in Experimental Models of Interstitial Cystitis/Bladder Pain Syndrome

Restoring the barrier of chronically damaged urothelium using chondroitin sulfate glycosaminoglycan-replenishment therapy

The urothelial barrier in interstitial cystitis/bladder pain syndrome: its form and function, an overview of preclinical models

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