Estrogen Inhibiting Drugs Show Promise in Muscular Dystrophy

Patients with muscular dystrophy (MD) experience significant physical symptoms that can result in a shortened lifespan. Despite the life-threatening nature of the disease, the only treatment is to reduce the cycle of inflammation and progression with steroids.

Selective estrogen receptor modulators (SERMs) may offer patients with MD a new treatment option. In a new study published by the American Journal of Pathology, the researchers showed that tamoxifen and raloxifene improved cardiac, respiratory, and muscle function among mice models of MD.

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The study also showed that SERM therapy improved bone density in animal models.

"Our results show that there are 2 important advantages of tamoxifen and raloxifene treatment over steroids, which have limited benefits for patients with MD,” said co-author Qi Long Lu, MD, PhD. “First, the SERMs improve both histology and function of all muscles; although steroids improve histology, they improve function to a much lesser extent. Second, SERMs enhance bone density, whereas steroids exacerbate osteoporosis and increase the risk for fractures.”

In the study, mice were administered tamoxifen, raloxifene, or saline for up to 1 year. The researchers used mice that have genetic defects nearly identical to humans with MD.

The authors noted that within 1 month, treatment with either drug reduced muscle pathology, as measured by the number of degenerating fibers, according to the study.

At 1 year, control mice had a significant variation in fiber size with focal inflammatory infiltration; however, treatment with either SERM reduced the occurrence of these changes, according to the study.

The authors also discovered that mice administered tamoxifen or raloxifene had a reduced accumulation of collagen in limb muscles.

Notably, SERM therapy was found to prevent damage and improve respiratory and cardiac muscles as well, according to the study.

The authors found that control mice demonstrated muscle degeneration of the diaphragm, followed by regeneration that increased fibrosis and infiltration, which impacted breathing. Treatment with tamoxifen and raloxifene was found to mitigate these events and improve breathing.

"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," said co-author Bo Wu, PhD.

Further, the SERM cohort improved grip strength and had improved running ability, depending on the dose, according to the study.

The researchers cautioned that sex-related differences in the drugs may call for additional studies to determine safety.

"SERM therapy has great potential to significantly delay or halt MD progression. With the vast amount of safety data available, the selective use of tamoxifen and raloxifene in male and female patients with MD is an attractive and realistic alternative to steroids," Dr Lu said.