Lerner Research Institute News
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Bimagrumab, a novel monoclonal antibody that enlarges muscle cells and builds muscle strength, has shown promise as a potential treatment for stress urinary incontinence (SUI). It’s the first muscle growth promoter to be studied for increasing urethral pressure and continence in an SUI model.
Currently, there are no medications available in the United States for treating SUI. Outside the US, treatments include pharmaceuticals that increase muscle tone, but none that increase muscle volume, like bimagrumab.
“Our lab study built on previous findings that SUI can be treated by increasing muscle tone of the urethra,” said Margot Damaser, PhD, a researcher in the Department of Biomedical Engineering and lead author on the study, which was published in the American Journal of Physiology – Renal Physiology. “Increasing muscle volume is another way to increase muscle tone and, therefore, muscle contraction.”
Comparing muscle growth promoters
The study evaluated the effect of three drugs in preclinical models of SUI, including: bimagrumab; a steroid-like drug approved in Japan for treating SUI, called clenbuterol; and a drug that works similarly to clenbuterol.
After two weeks of treatment, all three treatment groups had increases in body and muscle weight compared to the placebo group. Most notably, however, the models that received bimagrumab showed an approximate 10 percent increase in muscle weight, which was significantly more than the other treatment groups.
“The preclinical models of SUI were characterized by both nerve and muscle damage, which is hard to regenerate and can result in muscles wasting away—what we call atrophy,” said Dr. Damaser. “With bimagrumab, the pelvic muscles actually regenerated within two weeks of starting treatment.”
The drug also had a strong effect on components of the extracellular matrix (a network of molecules that provides structural support), which made the healed muscle look virtually normal. “Usually we see scarring when atrophied muscle heals, but that wasn’t the case with bimagrumab,” she said.
Pharmaceutical options are possible
This proof-of-concept test is the first of many more preclinical studies needed before introducing a clinical trial. There are many unanswered questions about long-term effects of this treatment and proper dosage, according to Dr. Damaser.
“We noted a gain in overall body weight with systemic bimagrumab,” she said. “Would that be acceptable for patients with SUI? Or could we localize treatment, limiting it to just the urethra and pelvic floor?”
Even without these answers, this initial study hints that the future of SUI treatment could include pharmaceutical options, potentially filling the gap between conservative measures like lifestyle modifications and pelvic floor exercises, and more advanced therapies like collagen injections and surgery.
“Although other pharmaceuticals tested in the past 20 years have not been successful in the US, there may be other viable options. Our early results with bimagrumab open up a new category of drugs for further evaluation.”
Jun Yang, PhD, a research associate in Dr. Damaser’s lab, was first author on the study, which was supported in part by the Novartis Institutes for BioMedical Research.