Yang, J, Balog, B, Deng , K, Hanzlicek, B, Rietsch, A, Kuang, M, Hatakeyama, Shinji, Trifilieff, Estelle, Zhu, H and Damaser, MS (2020) Therapeutic potential of muscle growth promoters in a stress urinary incontinence model. American Journal of Physiology-Renal Physiology, 319 (3). F436-F446. ISSN 1931-857X1522-1466

Abstract

Weakness of urinary sphincter and pelvic floor muscles can cause insufficient urethral closure and lead to stress urinary incontinence (SUI). Bimagrumab is a novel myostatin inhibitor which blocks activin type II receptors, inducing skeletal muscle hypertrophy and attenuating muscle weakness. β2-adrenergic agonists, such as 5-hydroxybenzothiazolone derivative (5-HOB) and clenbuterol can enhance muscle growth. We hypothesized that promoting muscle growth would increase urethral pressure by facilitating muscle recovery in a dual injury (DI) SUI model. Rats underwent pudendal nerve crush (PNC) followed by vaginal distension (VD). One week after injury, each rat began subcutaneous (0.3ml/rat) treatment daily in a blinded fashion with either bimagrumab (DI+Bim), clenbuterol (DI+Clen), 5-HOB (DI+5HOB) or phosphate-buffered saline (PBS, DI+Sham). Sham-injured rats underwent sham PNC+VD and received PBS (SI). After two weeks of treatment, the rats were anesthetized for leak point pressure (LPP) and external urethral sphincter (EUS) electromyography recordings. Hind limb skeletal muscles and pelvic floor muscles were dissected and stained. At the end of 2 weeks of treatment, all 3 treatment groups had a significant increase in body weight and individual muscle weight compared to both sham treated and sham-injured rats. LPP in the DI+Bim group was significantly higher than LPP of DI+sham and DI+Clen rats. There were more consistent urethral striated muscle fibers, elastin fibers in the urethra and pelvic muscle recovery in DI+Bim rats compared with DI+Sham rats. In conclusion, bimagrumab was the most effective for increasing urethral pressure and continence by promoting injured EUS and pelvic floor muscle recovery.

Item Type:	Article
Date Deposited:	30 Dec 2020 00:45
Last Modified:	30 Dec 2020 00:45
URI:	https://oak.novartis.com/id/eprint/42303