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Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome

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Abstract

Introduction

Overactive Bladder Syndrome (OAB) significantly impacts quality of life, necessitating improved diagnostic tools and treatment monitoring. This study explores the potential of neurotrophins, nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) as urinary biomarkers in patients with OAB undergoing mirabegron therapy, a β3-adrenergic agonist. This investigation is aimed at providing insights into the potential of neurotrophins to enhance OAB diagnosis and assess treatment efficacy.

Materials and Methods

Urinary NGF and BDNF levels were measured in 15 healthy controls and 30 patients with OAB. Patients were treated with mirabegron 50 mg once daily. Urinary NGF and BDNF levels were measured by enzyme-linked immunosorbent assay method and normalized by urinary creatinine levels (NGF/Cre and BDNF/Cre). The urinary NGF/Cre and BDNF/Cre levels were compared between controls and patients with OAB and subsequently at baseline and 3 months after mirabegron treatment. Treatment efficacy was assessed with the Indevus Urgency Severity Scale (IUSS) questionnaire.

Results

Urinary NGF/Cre and BDNF/Cre levels were significantly higher in patients with OAB than in the controls (p < 0.001 and p = 0.03 respectively). Moreover, NGF/Cre and BDNF/Cre levels significantly decreased post-mirabegron treatment (p < 0.001 and p = 0.005 respectively). Patients with improvement of OAB symptoms after treatment showed lower levels of NGF/Cre at the 3-month evaluation than those with no improvement (p = 0.05).

Conclusion

Although both NGF/Cre and BDNF/Cre levels were significantly decreased after mirabegron treatment, only NGF/Cre levels were associated with treatment response.

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Data Availability

The research data are available upon request.

Abbreviations

BDNF:

Brain-derived neurotrophic factor

BMI:

Body mass index

Cre:

Creatinine

DO:

Detrusor overactivity

IUSS:

Indevus Urgency Severity Scale

IQR:

Interquartile range

LUTS:

Lower urinary tract symptoms

NGF:

Nerve growth factor

OAB:

Overactive bladder

SD:

Standard deviation 

UTI:

Urinary tract infection

References

  1. Abrams P, Cardozo L, Fall M, et al. The standardisation of terminology in lower urinary tract function: report from the standardisation sub-committee of the International Continence Society. Urology. 2003;61(1):37–49.

    Article  PubMed  Google Scholar 

  2. Stewart WF, Van Rooyen JB, Cundiff GW, et al. Prevalence and burden of overactive bladder in the United States. World J Urol. 2003;20(6):327–36.

    Article  CAS  PubMed  Google Scholar 

  3. Haylen BT, de Ridder D, Freeman RM, et al. An International Urogynecological Association (IUGA)/International Continence Society (ICS) joint report on the terminology for female pelvic floor dysfunction. Int Urogynecol J. 2010;21(1):5–26.

    Article  PubMed  Google Scholar 

  4. Drake MJ. Do we need a new definition of the overactive bladder syndrome? ICI-RS 2013. Neurourol Urodyn. 2014;33(5):622–4.

    Article  PubMed  Google Scholar 

  5. McGuire E. Bladder instability and stress incontinence. Neurourol Urodyn. 1988;7(6):563–7.

    Article  Google Scholar 

  6. Bates CP, Bradley WE, Glen ES, et al. Third Report on the Standardisation of Terminology of Lower Urinary Tract Function: procedures related to the evaluation of micturition: pressure-flow relationships. Residual urine. Br J Urol. 1980;52(5):348–50.

    Article  Google Scholar 

  7. Robinson D, Thiagamoorthy G, Cardozo L. A drug safety evaluation of mirabegron in the management of overactive bladder. Expert Opin Drug Saf. 2016;15(5):689–96.

    Article  CAS  PubMed  Google Scholar 

  8. Mirabegron. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda, MD: National Institute of Diabetes and Digestive and Kidney Diseases; 2012. Accessed 2 September 2023. Available from: http://www.ncbi.nlm.nih.gov/books/NBK547887/

  9. Yoshida M, Masunaga K, Nagata T, Yono M, Homma Y. The forefront for novel therapeutic agents based on the pathophysiology of lower urinary tract dysfunction: pathophysiology and pharmacotherapy of overactive bladder. J Pharmacol Sci. 2010;112(2):128–34.

    Article  CAS  PubMed  Google Scholar 

  10. Cruz CD. Neurotrophins in bladder function: what do we know and where do we go from here? Neurourol Urodyn. 2014;33(1):39–45.

    Article  CAS  PubMed  Google Scholar 

  11. Ochodnicky P, Cruz CD, Yoshimura N, Cruz F. Neurotrophins as regulators of urinary bladder function. Nat Rev Urol. 2012;9(11):628–37.

    Article  CAS  PubMed  Google Scholar 

  12. Ochodnický P, Cruz CD, Yoshimura N, Michel MC. Nerve growth factor in bladder dysfunction: contributing factor, biomarker, and therapeutic target. Neurourol Urodyn. 2011;30(7):1227–41.

    Article  PubMed  Google Scholar 

  13. Nixon A, Colman S, Sabounjian L, et al. A validated patient reported measure of urinary urgency severity in overactive bladder for use in clinical trials. J Urol. 2005;174(2):604–7. https://doi.org/10.1097/01.ju.0000165461.38088.7b.

    Article  PubMed  Google Scholar 

  14. Steers WD. Pathophysiology of overactive bladder and urge urinary incontinence. Rev Urol. 2002;4(Suppl 4):S7–18.

    PubMed  PubMed Central  Google Scholar 

  15. Coelho A, Oliveira R, Antunes-Lopes T, Duarte Cruz C. Partners in crime: NGF and BDNF in visceral dysfunction. Curr Neuropharmacol. 2019;17(11):1021–38. https://doi.org/10.2174/1570159X17666190617095844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yuk SM, Shin JH, Song KH, Na YG, Lim JS, Sul CK. Expression of brain derived-neurotrophic factor and granulocyte-colony stimulating factor in the urothelium: relation with voiding function. BMC Urol. 2015;15:37. https://doi.org/10.1186/s12894-015-0036-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Cheng C, Li Q, Lin G, Opara EC, Zhang Y. Neurobiological insights into lower urinary tract dysfunction: evaluating the role of brain-derived neurotrophic factor. Am J Clin Exp Urol. 2023;11(6):559–77

    PubMed  PubMed Central  Google Scholar 

  18. Kashyap MP, Pore SK, de Groat WC, Chermansky CJ, Yoshimura N, Tyagi P. BDNF overexpression in the bladder induces neuronal changes to mediate bladder overactivity. Am J Physiol Renal Physiol. 2018;315(1):F45–56.

    Article  CAS  PubMed  Google Scholar 

  19. Tsiapakidou S, Apostolidis A, Pantazis K, Grimbizis GF, Mikos T. The use of urinary biomarkers in the diagnosis of overactive bladder in female patients. A systematic review and meta-analysis. Int Urogynecol J. 2021;32(12):3143–55.

    Article  PubMed  Google Scholar 

  20. Liu HT, Chen CY, Kuo HC. Urinary nerve growth factor in women with overactive bladder syndrome. BJU Int. 2011;107(5):799–803.

    Article  CAS  PubMed  Google Scholar 

  21. Antunes-Lopes T, Pinto R, Barros SC, et al. Urinary neurotrophic factors in healthy individuals and patients with overactive bladder. J Urol. 2013;189(1)):359–65. https://doi.org/10.1016/j.juro.2012.08.187

    Article  CAS  PubMed  Google Scholar 

  22. Suh YS, Ko KJ, Kim TH, et al. Urinary nerve growth factor as a potential biomarker of treatment outcomes in overactive bladder patients. Int Neurourol J. 2017;21(4):270–81.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sağır S, Bayrak Ö, Şen H, Kul S, Erturhan S, Seçkiner İ. Correlation between the NGF levels and questionnaire forms in patients receiving antimuscarinic treatment and those receiving onabotulinum toxin-A injection. Turk J Urol. 2021;47(3):223–8.

    Article  PubMed  Google Scholar 

  24. Birder LA, Wolf-Johnston AS, Sun Y, Chai TC. Alteration in TRPV1 and Muscarinic (M3) receptor expression and function in idiopathic overactive bladder urothelial cells. Acta Physiol (Oxf). 2013;207(1):123–9.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. 2nd Department of Obstetrics and Gynecology, Athens University, Medical School, Aretaieion Hospital, Vasilissis Sofias Avenue, 76, 11528, Athens, PC, Greece

    Anastasia Beta, Aikaterini Giannouli, Demetrios Rizos & Panagiotis Bakas

  2. Division of Endocrinology, Metabolism, and Diabetes, First Department of Pediatrics, School of Medicine, National and Kapodistrian University of Athens, Aghia Sophia Children’s Hospital, 11527, Athens, Greece

    Aimilia Mantzou

  3. Department of Pediatric & Adolescent Gynecology, Mitera Children’s Hospital, 15123, Athens, Greece

    Efthymios Deligeoroglou

Authors
  1. Anastasia Beta
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  2. Aikaterini Giannouli
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  3. Demetrios Rizos
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  4. Aimilia Mantzou
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  5. Efthymios Deligeoroglou
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  6. Panagiotis Bakas
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Contributions

A.B.: conceptualization, methodology, formal analysis, investigation, data curation, resources, writing—original draft preparation, visualization; A.G.: formal analysis, data curation, writing—original draft preparation, visualization; D.R.: methodology, formal analysis, resources, writing—review and editing, supervision; A.M.: methodology, formal analysis, resources; E.D.: methodology, resources, writing—review and editing, supervision; P.B.: conceptualization, methodology, investigation, resources, writing—review and editing, visualization, supervision.

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Correspondence to Anastasia Beta.

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Beta, A., Giannouli, A., Rizos, D. et al. Nerve Growth Factor and Brain-Derived Neurotrophic Factor as Potential Biomarkers of Mirabegron Efficacy in Patients with Overactive Bladder Syndrome. Int Urogynecol J (2024). https://doi.org/10.1007/s00192-024-05809-0

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  • DOI: https://doi.org/10.1007/s00192-024-05809-0

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