New Pill Replicates Exercise and Strengthens Muscle

Fitness Man Upper Body Strength Energy

Researchers discovered that the drug induces similar effects to exercise.

A drug has been identified by researchers at Tokyo Medical and Dental University (TMDU) that replicates the benefits of exercise on mice’s bones and muscles.

You can look and feel better by keeping up a regular exercise schedule, but did you know that exercise also supports bone and muscle health? Locomotor fragility, which affects people who are unable to exercise, causes the muscles and bones to deteriorate. Recently, Japanese researchers discovered a new drug that, by producing effects comparable to those of exercise, may help treat locomotor frailty.

Physical inactivity can result in a weakening of the muscles (known as sarcopenia) and bones (known as osteoporosis). Exercise dispels this frailty by boosting muscular strength and suppressing bone resorption while simultaneously promoting bone formation. Exercise therapy, however, cannot be used in every clinical situation. When patients have dementia, cerebrovascular disease, or are already bedridden, drug therapy may be very helpful for treating sarcopenia and osteoporosis. However, there is no one drug that targets both tissues at the same time.

LAMZ Locomomimetic Drug

Exercise induces calcium signaling in the muscle and bones. Under this signaling, PGC-1α is activated, resulting in the augmentation of these tissues. LAMZ, a newly identified locomomimetic drug was found to facilitate the calcium signaling pathway and restores locomotor fitness. Credit: Department of Cell Signaling, TMDU

Researchers from Tokyo Medical and Dental University (TMDU) used a novel drug screening system in a recent study that was published in the journal Bone Research to identify a compound that replicates the changes in muscle and bone that arise from exercise. Using the screening system, the researchers discovered the aminoindazole derivative locamidazole (LAMZ). LAMZ has the ability to stimulate the growth of bone-forming osteoblasts and muscle cells while inhibiting the formation of osteoclasts, which break down bone.

LAMZ was successfully transmitted into the bloodstream of mice when administered orally, with no evident side effects. Takehito Ono, the study’s lead author, stated, “We were pleased to find that LAMZ-treated mice exhibited larger muscle fiber width, greater maximal muscle strength, a higher rate of bone formation, and lower bone resorption activity.”

The research team further addressed the mode of function of LAMZ and found that LAMZ mimics calcium and PGC-1α signaling pathways. These pathways are activated during exercise and stimulate the expression of downstream molecules that are involved in the maintenance of muscle and bone.

To investigate whether LAMZ can treat locomotor frailty, LAMZ was administrated to an animal model of sarcopenia and osteoporosis. “Both oral and subcutaneous administration of the drug improved the muscle and bone of mice with locomotor frailty,” says senior author Tomoki Nakashima.

Taken together, the research team’s findings show that LAMZ represents a potential therapeutic method for the treatment of locomotor frailty by mimicking exercise.

Reference: “Simultaneous augmentation of muscle and bone by locomomimetism through calcium-PGC-1α signaling” by Takehito Ono, Ryosuke Denda, Yuta Tsukahara, Takashi Nakamura, Kazuo Okamoto, Hiroshi Takayanagi, and Tomoki Nakashima, 3 August 2022, Bone Research.
DOI: 10.1038/s41413-022-00225-w

The study was funded by the Japan Science and Technology Agency, the Japan Agency for Medical Research and Development, the Japanese Ministry of Education, Culture, Sports, Science and Technology, JAPAN, the Daiichi Sankyo Foundation of Life Science, the Takeda Science Foundation, and the Secom Science and Technology Foundation. 

New Pill Replicates Exercise and Strengthens Muscle