New pill replicates exercise and builds muscle

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

You can look and feel better by following a regular exercise program, but did you know that exercise also promotes healthy bones and muscles? Locomotor frailty, which affects people unable to exercise, leads to deterioration of muscles and bones. Recently, Japanese researchers discovered a new drug which, by producing effects comparable to those of exercise, could help treat locomotor fragility.

Muscles and bones can become weak due to physical inactivity, a condition known as sarcopenia (known as osteoporosis). Exercise dispels this frailty by increasing muscle strength and suppressing bone resorption while simultaneously promoting bone formation. Exercise therapy, however, cannot be used in all clinical situations. When patients have dementia, cerebrovascular disease, or are already bedridden, drug therapy can be very helpful in treating sarcopenia and osteoporosis. However, no drug targets both tissues at the same time.

Exercise induces calcium signaling in muscle and bone. Under this signaling, PGC-1α is activated, causing these tissues to increase. LAMZ, a newly identified locomotive drug, has been shown to facilitate the calcium signaling pathway and restore locomotor ability. Credit: Cell Signaling Department, TMDU

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

LAMZ was successfully transmitted into the bloodstream of mice when given orally, with no obvious side effects. Takehito Ono, the study’s lead author, said, “We were delighted to find that LAMZ-treated mice exhibited greater muscle fiber width, greater peak muscle strength, bone formation rate higher and lower bone resorption activity.

The research team then looked at how LAMZ works and found that LAMZ mimics calcium and PGC-1α signaling pathways. These pathways are activated during exercise and stimulate the expression of downstream molecules involved in maintaining muscle and bone.

To determine if LAMZ can treat locomotor frailty, LAMZ was administered to an animal model of sarcopenia and osteoporosis. “Oral and subcutaneous administration of the drug improved the muscles and bones of mice with locomotor frailty,” says lead author Tomoki Nakashima.

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

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

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