Old drugs are new! Tamoxifen and raloxifene significantly delay the progression of muscular dystrophy

2023-10-17 01:07:45

March 26, 2018 Source: Sina Pharmaceutical

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Recently, researchers from the Carolina Medical Center in the United States have confirmed that long-term treatment with selective estrogen receptor modulators (SERMs) tamoxifen or raloxifene can delay the most common type of muscle. Disease progression in mice with malnutrition (MD) models. The results showed that male and female model mice improved their heart, respiratory, and skeletal muscle functions and increased bone density after one year of treatment with this therapy.

The study has been published in the international medical journal American Pathology. The study's lead researcher, Dr. QI-Long Lu, said that our findings suggest that tamoxifen and raloxifene SERM therapy have two important advantages over steroid therapy, and steroid therapy has limited benefit for MD patients. First, SERM can improve the histology and function of all muscles at the same time; although steroid therapy can improve histology, they improve muscle function much less. Second, SERM can increase bone density, and steroid therapy can aggravate osteoporosis and increase fracture risk.

SERM is widely used because of its anti-inflammatory, anti-fibrosis, bone loss prevention, and muscle strengthening. This is also a feature of muscular dystrophy. Steroids are currently the only treatments available to reduce the cycle of inflammation and functional deterioration in MD patients.

Anti-muscle atrophy-associated glycoproteinosis (DG) is the third most common type of limb-type muscular dystrophy caused by mutations in the Fukutin-related protein gene (FKRP). To investigate whether SERM can help reduce this MD type of pathology and delay disease progression, the Carolina Medical Center McColllock Wood Laboratory team tested two SERMs, one for the breast cancer treatment tamoxifen, another Raloxifene, a drug commonly used to prevent and treat bone loss in postmenopausal women, is an oral therapy for FKRP P448L mutant mice that carry the same genetic mutations in humans that cause this type of MD. In the study, model mice were treated with oral tamoxifen or raloxifene for 3 years from 3 weeks of age.

The results showed that treatment significantly improved disease progression, including increased grip production, running time and distance in treadmill testing. Histological analysis confirmed that the model mice exhibited reduced muscle pathology and a lesser number of degraded muscle fibers within one month of initiation of any of the SERM treatments. After one year of treatment, the SERM treatment group showed less dystrophic changes in muscle fibers, and the muscle collagen accumulation in the limbs also showed a parallel decrease. In addition to reducing skeletal muscle damage, SERM therapy also enhances the function of the respiratory muscles and myocardium.

This is the effect of one year of tamoxifen and raloxifene treatment on muscle function (by grip strength and treadmill exercise)

And fibrosis shown by Masson's trichrome staining of the tibialis anterior muscle.

(Tan and T) Tamoxifen; (Ral and R) raloxifene. [The American Journal of Pathology]

In the SERM-treated group, tamoxifen and raloxifene reduced the degree of diaphragmatic fiber damage and increased the amount of diaphragm muscle and improved breathing. Both drugs also improved bone density in the tibia and femur and potentially reduced the risk of fracture.

The researchers also noted that there was a gender difference in treatment: tamoxifen had a serious adverse effect on the male reproductive organs, and raloxifene did not. The researchers concluded that tamoxifen and raloxifene have significant potential for the treatment of FKRP-associated MD and possibly other types of MD. The gender differential effect of drugs requires careful consideration of drug and dose selection in the male and female patient populations.

According to Dr. QI-Long Lu, SERM therapy has the potential to significantly delay or halt the progression of MD. Based on the currently available clinical safety data for tamoxifen and raloxifene, selective use of tamoxifen and raloxifene is an attractive alternative to steroid therapy in both male and female MD patients. Force and practical meaning of medication choices. The authors believe that the beneficial effects of SERM may also extend to other types of MD. (Sina Pharmaceutical Compilation/newborn)

Article reference source: Tamoxifen and Raloxifene Slow Progression of Muscular Dystrophy

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