A New Potential Treatment to Decrease the Progression of Muscular Dystrophy Has Been Discovered

Copa Show blog post 1

A recently study in the American Journal of Pathology has revealed a new way to approach and treat patients suffering with muscular dystrophy (MD). The study found that using the selective estrogen receptor modulators (SERMs) tamoxifen and raloxifene considerably improved cardiac, respiratory, and skeletal muscle functions and increased bone density in both male and female mice with the same gene defects as a subset of patients with MD.

The mice that were used in this study were picked based on the whether they had the same gene defect and a similar type of disease manifestation as the patients with MD. Investigators administered tamoxifen (2, 10, or 50 mg/kg), raloxifene (50 or 100 mg/kg), or saline to mutant mice with dystroglycanopathy, a form of MD, for up to a year, beginning at three weeks of age.

“Two advantages of tamoxifen and raloxifene treatment over the usual steroid treatment have been highlighted within our study. Steroids have limited benefits for patients with MD so this study could potentially change the way we treat MD. The first advantage we discovered was that SERMs improved the histology and function of all muscles. Secondly, SERMs enhanced bone density, whereas steroids exacerbate osteoporosis and increase the risk for fractures," explained Qi Long Lu, MD, PhD, director of the McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Department of Neurology, Atrium Health's (formerly Carolinas HealthCare System's) Carolinas Medical Center, Charlotte (NC).

The study also recorded that there were several indicators that tamoxifen and raloxifene could delay or even stop disease progression. After just one month the mice that had been treated with SERM had reduced muscle pathology and the number of degenerating fibres were also reduced.

After a year, the control mice were found to have a extensive variation of fibre size with focal inflammatory infiltrations. However, when the mice were treated with tamoxifen or raloxifene, these dystrophic changes were much less apparent. 

A reduction of collagen accumulation in limb muscles was reported for all treatment groups. This shows us that SERMS alleviates muscle damage whilst also enhancing the functions of cardiac and respiratory muscles.

Co-author Bo Wu, PhD, a research scientist at the McColl-Lockwood Laboratory for Muscular Dystrophy Research, Neuromuscular/ALS Center, Department of Neurology, Atrium Health's (formerly Carolinas HealthCare System's) Carolinas Medical Center, Charlotte (NC) discussed some of the other benefits that were discovered, she said "both treatments also improved bone density in the tibia and femur, potentially reducing the risk of fracture, a major threat to patients as MD progresses.”

Functional improvements were also observed, as the SERM treatment improved grip strength for the forelimb and hindlimb muscles, and running ability showed signs of improvement when the treatment group where partaking in the treadmill test, but these results were dependent on the dose they were given.

Because SERMs act on estrogen receptors and interact both as estrogen-receptor agonists and antagonists, using tamoxifen and raloxifene warrant careful consideration if the drugs are to be administered clinically for MD.

With these results, SERM therapy can be seen as a realistic and alternative therapy to steroids, and the beneficial effects of SERMs are predicted to branch into other forms of MD.