Comparison of Efficacy of Neovasculgen® and Botox® in the treating Interstitial Cystitis/Bladder Pain Syndrome: experimental study

Introduction. Interstitial cystitis/bladder pain syndrome (IC/BPS), being a chronic non-infectious disease, still has an unclear etiology and numerous pathophysiological theories of development. This determines the need for preclinical experimental studies on animals. The most identical model of human IC/BPS is cyclophosphamide-induced cystitis in rodents.

Objective. To study the effects of the pharmacological activity of Neovasculgen® сompared to Botox® using model of cyclophosphamide-induced IC/BPS in rats.

Materials & methods. The study was performed on 90 female Wistar rats. IC/BPS was induced by Endoxan®. Neovasculgen® and Botox® were used as intradetrusor therapeutic agents. Efficiency was assessed by comparative analysis of urodynamic patterns and morphologically. The data obtained were processed by parametric and nonparametric methods of statistical analysis.

Results. Cyclophosphamide-induced IC/BPS developed in all animals. Both drugs statistically significantly improved the studied urodynamic parameters, the clinical efficacy of Neovasculgen® was comparable to Botox®. Morphological assessment showed that the administration of the studied drugs was accompanied by a decrease in tissue edema, less pronounced hemorrhages and focal lymphohistiocytic infiltration, as well as destructive changes in the bladder mucosa. At the same time, the intensity of pathological tissue processes against the background of the administration of Neovasculgen® was the lowest.

Conclusions. The cyclophosphamide-induced IC/BPS model is considered the most adequate human IC/BPS. The experiment is extremely important for studying the effectiveness of a new drug, which is intradetrusor Neovasculgen®. The drug has shown its effectiveness in reducing the frequency of urination and intravesical pressure. Intradetrusor administration reduces the severity of the inflammatory reaction of bladder tissue.

1. Hanno PM, Erickson D, Moldwin R, Faraday MM; American Urological Association. Diagnosis and treatment of interstitial cystitis/bladder pain syndrome: AUA guideline amendment. J Urol. 2015;193(5):1545-1553. DOI: 10.1016/j.juro.2015.01.086

2. Parsons CL. The role of the urinary epithelium in the pathogenesis of interstitial cystitis/prostatitis/urethritis. Urology. 2007;69(4 Suppl):9-16. DOI: 10.1016/j.urology.2006.03.084

3. de Groat WC, Griffiths D, Yoshimura N. Neural control of the lower urinary tract. Compr Physiol. 2015;5(1):327-396. DOI: 10.1002/cphy.c130056

4. Karamali M, Shafabakhsh R, Ghanbari Z, Eftekhar T, Asemi Z. Molecular pathogenesis of interstitial cystitis/bladder pain syndrome based on gene expression. J Cell Physiol. 2019;234(8):12301-12308. DOI: 10.1002/jcp.28009

5. Akiyama Y. Biomarkers in Interstitial Cystitis/Bladder Pain Syndrome with and without Hunner Lesion: A Review and Future Perspectives. Diagnostics (Basel). 2021;11(12):2238. DOI: 10.3390/diagnostics11122238

6. Shah AM, Vodovotz Y, Yoshimura N, Chermansky CJ, Fitzgerald J, Tyagi P. Temporally complex inflammatory networks in an animal model reveal signatures for interstitial cystitis and bladder pain syndrome phenotype. Neurourol Urodyn. 2023;42(8):1839-1848. DOI: 10.1002/nau.25267

7. Akiyama Y, Luo Y, Hanno PM, Maeda D, Homma Y. Interstitial cystitis/ bladder pain syndrome: The evolving landscape, animal models and future perspectives. Int J Urol. 2020;27(6):491-503. DOI: 10.1111/iju.14229

8. Chang YC, Yu CY, Dong C, Chen SL, Sung WW. Divergent histopathological and molecular patterns in chemically induced interstitial cystitis/bladder pain syndrome rat models. Sci Rep. 2024;14(1):16134. DOI: 10.1038/s41598-024-67162-y

9. Fowler CJ, Griffiths D, de Groat WC. The neural control of micturition. Nat Rev Neurosci. 2008;9(6):453-466. DOI: 10.1038/nrn2401

10. Garzon S, Laganà AS, Casarin J, Raffaelli R, Cromi A, Sturla D, Franchi M, Ghezzi F. An update on treatment options for interstitial cystitis. Prz Menopauzalny. 2020;19(1):35-43. DOI: 10.5114/pm.2020.95334

11. Khamedov R.G., Gorgotsky I.A., Shkarupa A.G., Shkarupa D.D., Gadzhiev N.K. Platelet-rich plasma: application for interstitial cystitis and erectile dysfunction. Urology Herald. 2022;10(1):121-127. (In Russian). DOI: 10.21886/2308-6424-2022-10-1-121-127

12. Chen YH, Man KM, Chen WC, Liu PL, Tsai KS, Tsai MY, Wu YT, Chen HY. Platelet-Rich Plasma Ameliorates Cyclophosphamide-Induced Acute Interstitial Cystitis/Painful Bladder Syndrome in a Rat Model. Diagnostics (Basel). 2020;10(6):381. DOI: 10.3390/diagnostics10060381

13. Brandolini L, Aramini A, Bianchini G, Ruocco A, Bertini R, Novelli R, Angelico P, Valsecchi AE, Russo R, Castelli V, Cimini A, Allegretti M. Inflammation-Independent Antinociceptive Effects of DF2755A, a CXCR1/2 Selective Inhibitor: A New Potential Therapeutic Treatment for Peripheral Neuropathy Associated to Non-Ulcerative Interstitial Cystitis/Bladder Pain Syndrome. Front Pharmacol. 2022;13:854238. DOI: 10.3389/fphar.2022.854238

14. Sakata T, Smith RA, Garland EM, Cohen SM. Rat urinary bladder epithelial lesions induced by acrolein. J Environ Pathol Toxicol Oncol. 1989;9(2):159-169. PMID: 2732910.

15. Bjorling DE, Elkahwaji JE, Bushman W, Janda LM, Boldon K, Hopkins WJ, Wang ZY. Acute acrolein-induced cystitis in mice. BJU Int. 2007;99(6):1523-1529. DOI: 10.1111/j.1464-410X.2007.06773.x

16. State Register of Medicines. Registration certificate of the drug Neovasculgen ® (Accessed 03.01.2025). (In Russian). URL: https://grls.rosminzdrav.ru/Grls_View_v2.aspx?routingGuid=fbd48945-f006-43d5-b67d-99825a786c08

17. Cherviakov IuV, Staroverov IN, Nersesian EG, Vlasenko ON, Isaev AA. The opportunities for genic therapy of chronic obliterating diseases of lower limbs arteries. Pirogov Russian Journal of Surgery. 2014;(4):40-45. (In Russian). eLIBRARY ID: 21568109; EDN: SDZIWN

18. Lucioni A, Bales GT, Lotan TL, McGehee DS, Cook SP, Rapp DE. Botulinum toxin type A inhibits sensory neuropeptide release in rat bladder models of acute injury and chronic inflammation. BJU Int. 2008;101(3):366-370. DOI: 10.1111/j.1464-410X.2007.07312.x

19. Birder L, Andersson KE. Animal Modelling of Interstitial Cystitis/Bladder Pain Syndrome. Int Neurourol J. 2018;22(Suppl 1):S3-9. DOI: 10.5213/inj.1835062.531

20. Gad SC, Spainhour CB, Shoemake C, Pallman DR, Stricker-Krongrad A, Downing PA, Seals RE, Eagle LA, Polhamus K, Daly J. Tolerable Levels of Nonclinical Vehicles and Formulations Used in Studies by Multiple Routes in Multiple Species With Notes on Methods to Improve Utility. Int J Toxicol. 2016;35(2):95-178. DOI: 10.1177/1091581815622442

21. Ruengwanichayakun P. Histochemical scoring assessment (H-score). Asian Arch Pathol. 2021;3(1):13–14.

22. Tay C, Grundy L. Animal models of interstitial cystitis/bladder pain syndrome. Front Physiol. 2023;14:1232017. DOI: 10.3389/fphys.2023.1232017

23. Mykoniatis I, Tsiakaras S, Samarinas M, Anastasiadis A, Symeonidis EN, Sountoulides P. Monoclonal Antibody Therapy for the Treatment of Interstitial Cystitis. Biologics. 2022;16:47-55. DOI: 10.2147/BTT.S290286

24. Ha JY, Lee EH, Chun SY, Lee JN, Ha YS, Chung JW, Yoon BH, Jeon M, Kim HT, Kwon TG, Yoo ES, Kim BS. The Efficacy and Safety of a Human Perirenal Adipose Tissue-Derived Stromal Vascular Fraction in an Interstitial Cystitis Rat Model. Tissue Eng Regen Med. 2023;20(2):225-237. DOI: 10.1007/s13770-022-00505-w

25. Jhang JF, Yu WR, Kuo HC. Comparison of the Clinical Efficacy and Adverse Events between Intravesical Injections of Platelet-Rich Plasma and Botulinum Toxin A for the Treatment of Interstitial Cystitis Refractory to Conventional Treatment. Toxins (Basel). 2023;15(2):121. DOI: 10.3390/toxins15020121

26. Lee YK, Jiang YH, Jhang JF, Ho HC, Kuo HC. Changes in the Ultrastructure of the Bladder Urothelium in Patients with Interstitial Cystitis after Intravesical Injections of Platelet-Rich Plasma. Biomedicines. 2022;10(5):1182. DOI: 10.3390/biomedicines10051182

27. Danacioglu YO, Erol B, Ozkanli S, Yildirim A, Atis RG, Silay MS, Caskurlu T. Comparison of Intravesical Hyaluronic Acid, Chondroitin Sulfate, and Combination of Hyaluronic Acid-Chondroitin Sulfate Therapies in Animal Model of Interstitial Cystitis. Int Neurourol J. 2021;25(1):42-50. DOI: 10.5213/inj.1938176.088