Tamoxifen and Evista Improved Muscle, Other MD Functions in Mouse Study

Tamoxifen and Evista Improved Muscle, Other MD Functions in Mouse Study

The use of tamoxifen and Evista (raloxifene) improved cardiac, respiratory, and skeletal muscle functions, and increased bone density in a mouse model of muscular dystrophy (MD), research from the Carolinas Medical Center suggests.

The study, “Long-Term Treatment of Tamoxifen and Raloxifene Alleviates Dystrophic Phenotype and Enhances Muscle Functions of FKRP Dystroglycanopathy,” appeared in The American Journal of Pathology.

Tamoxifen and Evista belong to a class of medications known as SERMS (selective estrogen receptor modulators), which have been used for the treatment of breast cancer, osteoporosis, and postmenopausal symptoms, due to their anti-inflammatory, prevention of bone loss, and muscle increasing properties.

Currently, steroids are the only available treatment for the repetitive inflammation and disease worsening in MD patients.

Using a mouse model of dystroglycanopathy, a specific type of MD characterized by weakness in arms and legs and caused by mutations in the FKRP gene, researchers evaluated the potential benefit of treatment with tamoxifen and Evista.

The medications were administered in different doses for up to a year, beginning at 3 weeks of age.

Results revealed that, within one month, treatment with either drug decreased muscle disease, particularly the numbers of degenerating fibers. After one year, untreated (control) mice showed high variations in fiber size with inflammation. Treatment with tamoxifen or Evista significantly prevented these alterations.

Data also demonstrated reduced collagen build-up in limb muscles of mice taking the drugs, as well as less muscle injury of both respiratory and cardiac muscles.

Compared to control mice, treatment with the drugs also eliminated focal infiltration and decreased fibrosis (scarring) in the diaphragm, improving the animals’ respiratory function.

Treatment with either SERM also increased grip strength of both the front and back limb muscles, and enhanced running ability in a dose-dependent manner.

“Our results show that there are two important advantages of tamoxifen and raloxifene [Evista] treatment over steroids, which have limited benefits for patients with MD,” Qi Long Lu, an MD and PhD, the study’s senior author, said in a press release.

“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,” Lu said.

Bo Wu, PhD, the study’s first author, 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.”

As SERMs act on estrogen receptors, future studies should evaluate sex-related differences in their effectiveness, the investigators added.

“SERM therapy has great potential to significantly delay or halt MD progression,” Lu said. “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.”

“In summary, this study provides strong evidence that tamoxifen and raloxifene can be explored to treat dystroglycanopathy of both sex populations,” the investigators wrote. “The mechanisms for the observed therapeutic effect are almost certainly nondisease specific; thus, such treatment approach is likely applicable to muscular dystrophies in general.”

3 comments

  1. Janette Wallace says:

    I have been taking steroids for almost 6 months (now reducing monthly)
    I am suffering from leg back and arm pains that are getting worse

    • mario ciuffi says:

      I also have taken prednisone (75 mg/day)for one month and I have tapered this drug for 4 months till zero dose. My legs and arms are weakened absolutely more than that my pathology produced during previous 15 years.
      I do not realize why physicians sometimes inconsiderately use the steroids knowing side effects of these drugs.

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