Therapeutic potential of muscle growth promoters in a stress urinary incontinence model.

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.

American journal of physiology. Renal physiology. 2020 Jul 20 [Epub ahead of print]

Jun Yang, Brian M Balog, Kangli Deng, Brett Hanzlicek, Anna Rietsch, Mei Kuang, Shinji Hatakeyama, Estelle Lach-Trifilieff, Hui Zhu, Margot S Damaser

Department of Urology, Tongji Hospital, Huazhong University of Science and Technology, China., Department of Biomedical Engineering, Cleveland Clinic., Department of Biomedical Engineering, Cleveland Clinic Lerner Research Institute, United States., Advanced Platform Technology Center, Louis Stokes Cleveland VA Medical Center, United States., Glickman Urological and Kidney Institute, Cleveland Clinic., Novartis Institutes for Biomedical Research., Novartis Institutes for BioMedical Research, Novartis pharma AG, Switzerland., Glickman Urologic and Kidney Institute, Cleveland Clinic, United States.

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