Promising therapeutic targets for the treatment of urine storage dysfunction: what’s the status?

References

• Kreydin EI, Gomes CM, Cruz F. Current pharmacotherapy of overactive bladder. Int Braz J urol. 2021;47(6):1091–1107. doi: 10.1590/s1677-5538.ibju.2021.99.12
   PubMed Web of Science ®Google Scholar
• Andersson KE. Emerging drugs for the treatment of bladder storage dysfunction. Expert Opin Emerg Drugs. 2022;27(3):277–287. doi: 10.1080/14728214.2022.2113057
   PubMed Web of Science ®Google Scholar
• Joseph S, Maria SA, Peedicayil J. Drugs currently undergoing preclinical or clinical trials for the treatment of overactive bladder: a review. Curr Ther Res Clin Exp. 2022;96:100669. doi: 10.1016/j.curtheres.2022.100669
   PubMed Web of Science ®Google Scholar
• Michel MC, Cardozo L, Chermansky CJ, et al. Current and emerging pharmacological targets and treatments of urinary incontinence and related disorders. Pharmacol Rev. 2023;75(4):554–674. doi: 10.1124/pharmrev.121.000523
   PubMed Web of Science ®Google Scholar
• Andersson KE. TRP channels as lower urinary tract sensory targets. Med Sci (Basel). 2019;7(5):67. doi: 10.3390/medsci7050067
   PubMedGoogle Scholar
• Andersson KE. Agents in early development for treatment of bladder dysfunction - promise of drugs acting at TRP channels? Expert Opin Investig Drugs. 2019;28(9):749–755. doi: 10.1080/13543784.2019.1654994
   PubMed Web of Science ®Google Scholar
• Kudsi SQ, Piccoli BC, Ardisson-Araújo D, et al. Transcriptional landscape of TRPV1, TRPA1, TRPV4, and TRPM8 channels throughout human tissues. Life Sci. 2022;8:120977.
   Google Scholar
• Andersson KE, Behr-Roussel D, Denys P, et al. Acute intravesical capsaicin for the study of TRPV1 in the lower urinary tract: clinical relevance and potential for innovation. Med Sci (Basel). 2022;10(3):50. doi: 10.3390/medsci10030050
   PubMedGoogle Scholar
• Szallasi A, Resiniferatoxin. Resiniferatoxin: nature’s precision medicine to silence TRPV1-positive afferents. Int J Mol Sci. 2023;24(20):15042. doi: 10.3390/ijms242015042
   PubMed Web of Science ®Google Scholar
• Zhu K, Wang L, Liao T, et al. Progress in the development of TRPV1 small-molecule antagonists: novel strategies for pain management. Eur J Med Chem. 2023;9(261):115806.
   Google Scholar
• Garami A, Shimansky YP, Rumbus Z, et al. Hyperthermia induced by transient receptor potential vanilloid-1 (TRPV1) antagonists in human clinical trials: Insights from mathematical modeling and meta-analysis. Pharmacol Ther. 2020;208:107474. doi: 10.1016/j.pharmthera.2020.107474
   PubMed Web of Science ®Google Scholar
• Perkins ME, Vizzard MA. Transient receptor potential vanilloid type 4 (TRPV4) in urinary bladder structure and function. Curr Top Membr. 2022;89:95–138.
   PubMedGoogle Scholar
• Girard BM, Campbell SE, Perkins M, et al. TRPV4 blockade reduces voiding frequency, ATP release, and pelvic sensitivity in mice with chronic urothelial overexpression of NGF. Am J Physiol Renal Physiol. 2019 1;317(6):F1695–F1706. doi: 10.1152/ajprenal.00147.2019
   PubMed Web of Science ®Google Scholar
• Goyal N, Skrdla P, Schroyer R, et al. Clinical pharmacokinetics, safety, and tolerability of a novel, first-in-class TRPV4 ion channel inhibitor, GSK2798745, in healthy and heart failure subjects. Am J Cardiovasc Drugs. 2019;19(3):335–342. doi: 10.1007/s40256-018-00320-6
   PubMed Web of Science ®Google Scholar
• Mole S, Harry A, Fowler A, et al. Investigating the effect of TRPV4 inhibition on pulmonary-vascular barrier permeability following segmental endotoxin challenge. Pulm Pharmacol Ther. 2020;4:101977. doi: 10.1016/j.pupt.2020.101977
   Google Scholar
• Souza Monteiro de Araujo D, Nassini R, Geppetti P, et al. TRPA1 as a therapeutic target for nociceptive pain. Expert Opin Ther Targets. 2020;24(10):997–1008. doi: 10.1080/14728222.2020.1815191
   PubMed Web of Science ®Google Scholar
• Aizawa N, Fujita T. The TRPM8 channel as a potential therapeutic target for bladder hypersensitive disorders. J Smooth Muscle Res. 2022;58:11–21. doi: 10.1540/jsmr.58.11
   PubMedGoogle Scholar
• Watanabe S, Fujimori Y, Matsuzawa A, et al. KPR-5714, a selective transient receptor potential melastatin 8 antagonist, improves voiding dysfunction in rats with bladder overactivity but does not affect voiding behavior in normal rats. Neurourol Urodyn. 2022;41(6):1336–1343. doi: 10.1002/nau.24951
   PubMed Web of Science ®Google Scholar
• Andersson KE. Purinergic signalling in the urinary bladder. Auton Neurosci. 2015;191:78–81. doi: 10.1016/j.autneu.2015.04.012
   PubMed Web of Science ®Google Scholar
• Abreu-Mendes P, Pinto R, Oliveira PD. Systemic therapy for bladder pain syndrome/interstitial cystitis (BPS/IC): systematic review of published trials in the Last 5 Years. Curr Bladder Dysfunct Rep. 2020;15(3):192–202. doi: 10.1007/s11884-020-00592-2
   Web of Science ®Google Scholar
• Davenport AJ, Neagoe I, Bräuer N, et al. Eliapixant is a selective P2X3 receptor antagonist for the treatment of disorders associated with hypersensitive nerve fibers. Sci Rep. 2021 6;11(1):19877. doi: 10.1038/s41598-021-99177-0
   PubMed Web of Science ®Google Scholar
• Klein S, Gashaw I, Baumann S, et al. First-in-human study of eliapixant (BAY 1817080), a highly selective P2X3 receptor antagonist: tolerability, safety and pharmacokinetics. Br J Clin Pharmacol. 2022;88(10):4552–4564. doi: 10.1111/bcp.15358
   PubMed Web of Science ®Google Scholar
• McGarvey LP, Birring SS, Morice AH, et al. Efficacy and safety of gefapixant, a P2X3 receptor antagonist, in refractory chronic cough and unexplained chronic cough (COUGH-1 and COUGH-2): results from two double-blind, randomised, parallel-group, placebo-controlled, phase 3 trials. Lancet. 2022;399(10328):909–923. doi: 10.1016/S0140-6736(21)02348-5
   PubMed Web of Science ®Google Scholar
• Ewerton F, Cruz F, Kapp M, et al. Efficacy and safety of eliapixant in overactive bladder: the 12-week, randomised, Placebo-controlled phase 2a OVADER study. European Urology Focus. 2023;10(1):S2405–4569(23)00182–7.
   Google Scholar
• Andersson KE. Oxidative stress and its possible relation to lower urinary tract functional pathology. BJU Int. 2018;121(4):527–533. doi: 10.1111/bju.14063
   PubMed Web of Science ®Google Scholar
• Speich JE, Tarcan T, Hashitani H, et al. Are oxidative stress and ischemia significant causes of bladder damage leading to lower urinary tract dysfunction? Report from the ICI-RS 2019. Neurourol Urodyn. 2020;39(Suppl 3):S16–S22. doi: 10.1002/nau.24313
   PubMedGoogle Scholar
• Wu YH, Chueh KS, Chuang SM, et al. Bladder hyperactivity induced by oxidative stress and bladder ischemia: a review of treatment strategies with antioxidants. Int J Mol Sci. 2021 2;22(11):6014. doi: 10.3390/ijms22116014
   PubMed Web of Science ®Google Scholar
• de Rijk MM, Wolf-Johnston A, Kullmann AF, et al. Aging-associated changes in oxidative stress negatively impacts the urinary bladder urothelium. Int Neurourol J. 2022;26(2):111–118. doi: 10.5213/inj.2142224.112
   PubMed Web of Science ®Google Scholar
• Andersson KE. Oxidative stress and its relation to lower urinary tract symptoms. Int Neurourol J. 2022;26(4):261–267. doi: 10.5213/inj.2244190.095
   PubMed Web of Science ®Google Scholar
• Andersson KE. Oxidative stress and lower urinary tract symptoms: cause or consequence? BJU Int. 2019;123(5):749–750. doi: 10.1111/bju.14633
   PubMed Web of Science ®Google Scholar
• Birder LA, Wolf-Johnston A, Wein AJ, et al.Purine nucleoside phosphorylase inhibition ameliorates age-associated lower urinary tract dysfunctions. JCI Insight. 2020 15;5(20): e140109. doi: 10.1172/jci.insight.140109
   PubMed Web of Science ®Google Scholar
• Birder LA, Wolf-Johnston AS, Zabbarova I, et al. Hypoxanthine induces signs of bladder aging with voiding dysfunction and lower urinary tract remodeling. J Gerontol A Biol Sci Med Sci. 2023;18:glad171. doi: 10.1093/gerona/glad171
   Google Scholar
• Wu Q, Gurpinar A, Roberts M, et al. Identification of the NADPH oxidase (Nox) subtype and the source of superoxide production in the micturition centre. Biology. 2022;11(2):183.
   PubMedGoogle Scholar
• Malmgren A, Sjögren C, Uvelius B, et al. Cystometrical evaluation of bladder instability in rats with infravesical outflow obstruction. J Urol. 1987;137(6):1291–1294. doi: 10.1016/S0022-5347(17)44485-5
   PubMed Web of Science ®Google Scholar
• Andersson KE, Uvelius B. Changes in the rat urinary bladder after the relief of outflow obstruction – tracing targets for treatment of persistent symptoms in patients. Front Urol. 2022 Oct 20 Sec. Neurourology, Behavioural Urology, and Urodynamics Volume 2 - 2022. doi: 10.3389/fruro.2022.1027086
   Google Scholar
• Uvelius B, Andersson KE. Molecular and morphological characteristics of the de-obstructed rat urinary bladder-an update. Int J Mol Sci. 2022;23(19):11330. doi: 10.3390/ijms231911330
   PubMed Web of Science ®Google Scholar
• Fry CH, Chakrabarty B, Hashitani H, et al. New targets for overactive bladder-ICI-RS 2109. Neurourol Urodyn. 2020;39(Suppl 3):S113–S121. doi: 10.1002/nau.24228
   PubMedGoogle Scholar
• Rodriguez-Nieves JA, Macoska JA. Prostatic fibrosis, lower urinary tract symptoms, and BPH. Nat Rev Urol. 2013;10(9):546–550. doi: 10.1038/nrurol.2013.149
   PubMed Web of Science ®Google Scholar
• Chen L, Lv L, Zhang L, et al. Metformin ameliorates bladder dysfunction in a rat model of partial bladder outlet obstruction. Am J Physiol Renal Physiol. 2021;320(5):F838–F858. doi: 10.1152/ajprenal.00625.2020
   PubMed Web of Science ®Google Scholar
• Enevoldsen FC, Sahana J, Wehland M, et al. Endothelin receptor antagonists: status quo and future perspectives for targeted therapy. J Clin Med. 2020;9(3):824. doi: 10.3390/jcm9030824
   PubMed Web of Science ®Google Scholar
• Zhao M, Ding N, Wang H, et al. Activation of TRPA1 iN bladder suburothelial myofibroblasts counteracts TGF-β1-induced fibrotic changes. Int J Mol Sci. 2023;24(11):9501. doi: 10.3390/ijms24119501
   PubMed Web of Science ®Google Scholar
• Sandner P, Vakalopoulos A, Hahn MG, et al. Soluble guanylate cyclase stimulators and their potential use: a patent review. Expert Opin Ther Pat. 2021;31(3):203–222. doi: 10.1080/13543776.2021.1866538
   PubMed Web of Science ®Google Scholar
• Zabbarova IV, Ikeda Y, Kozlowski MG, et al. Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator. J Pathol. 2022;2022(4):442–454. doi: 10.1002/path.5859
   Google Scholar
• Chakrabarty B, Drake MJ, Kanai AJ, et al. Selective reduction of neurotransmitter release by cAMP-dependent pathways in mouse detrusor. Am J Physiol Regul Integr Comp Physiol. 2022;323(6):R889–R899. doi: 10.1152/ajpregu.00166.2022
   PubMed Web of Science ®Google Scholar
• Kanai AJ, Andersson KE, Birder LA, et al. Soluble guanylate cyclase activators to treat benign prostatic hyperplasia and associated LUTS. Continence (Amst). 2023;100699. doi: 10.1016/j.cont.2023.100699 Epub 2023 May 17. PMID: 37389026; PMCID: PMC10310070.
   PubMedGoogle Scholar
• Liang WL, Liang B. Soluble guanylate cyclase activators and stimulators in patients with heart failure. Curr Cardiol Rep. 2023;25(6):607–613. doi: 10.1007/s11886-023-01884-9
   PubMed Web of Science ®Google Scholar
• Malysz J, Petkov GV. Urinary bladder smooth muscle ion channels: expression, function, and regulation in health and disease. Am J Physiol Renal Physiol. 2020;319(2):F257–F283. doi: 10.1152/ajprenal.00048.2020
   PubMed Web of Science ®Google Scholar
• Orfali R, Albanyan N. Ca2+-Sensitive potassium channels. Molecules. 2023;28(2):885. doi: 10.3390/molecules28020885
   PubMed Web of Science ®Google Scholar
• Andersson KE, Christ GJ, Davies KP, et al. Gene therapy for overactive bladder: a review of BK-Channel α-subunit gene transfer. Ther Clin Risk Manag. 2021;17:589–599. doi: 10.2147/TCRM.S291798
   PubMed Web of Science ®Google Scholar
• Rovner E, Chai TC, Jacobs S, et al. Evaluating the safety and potential activity of URO-902 (hMaxi-K) gene transfer by intravesical instillation or direct injection into the bladder wall in female participants with idiopathic (non-neurogenic) overactive bladder syndrome and detrusor overactivity from two double-blind, imbalanced, placebo-controlled randomized phase 1 trials. Neurourol Urodyn. 2020;39(2):744–753. doi: 10.1002/nau.24272
   PubMed Web of Science ®Google Scholar
• Chen LC, Kuo HC. Pathophysiology of refractory overactive bladder. Low Urin Tract Symptoms. 2019;11(4):177–181. doi: 10.1111/luts.12262
   PubMed Web of Science ®Google Scholar
• Peyronnet B, Mironska E, Chapple C, et al. A comprehensive review of overactive bladder pathophysiology: on the way to tailored treatment. Eur Urol. 2019;75(6):988–1000. doi: 10.1016/j.eururo.2019.02.038
   PubMed Web of Science ®Google Scholar
• Serati M, Andersson KE, Dmochowski R, et al. Systematic review of combination drug therapy for non-neurogenic lower urinary tract symptoms. Eur Urol. 2019;75(1):129–168. doi: 10.1016/j.eururo.2018.09.029
   PubMed Web of Science ®Google Scholar
• Bapir R, Bhatti KH, Eliwa A, et al. Efficacy of overactive neurogenic bladder treatment: a systematic review of randomized controlled trials. Arch Ital Urol Androl. 2022;94(4):492–506. doi: 10.4081/aiua.2022.4.492
   PubMedGoogle Scholar
• Hood B, Andersson KE. Common theme for drugs effective in overactive bladder treatment: inhibition of afferent signaling from the bladder. Int J Urol. 2013;20(1):21–27. doi: 10.1111/j.1442-2042.2012.03196.x
   PubMed Web of Science ®Google Scholar