Key Points:
- Locomotor frailty, or the weakening of muscles and bones due to the inability to engage in physical activity, is a problem for those with cerebrovascular disease, dementia and other diseases.
- Researchers in Tokyo identified a drug that stimulates the growth of muscle cells and bone-forming cells, thus mimicking the effects of exercise.
- When tested, the drug improved both the muscle and bone of mice with locomotor frailty.
People who are unable to engage in physical activity, such as those with cerebrovascular disease or dementia, experience weakening of their muscles and bones, a condition known as locomotor frailty. While drug therapy exists to treat sarcopenia (weakening of the muscles) and osteoporosis (weakening of the bones) separately, there is no single drug that addresses both simultaneously.
In a new study published in Bone Research, researchers from Tokyo Medical and Dental University (TMDU) developed a novel drug screening system to identify a compound that mimics the changes in muscle and bone that occur as a result of exercise. Using the screening system, the researchers identified aminoindazole derivative locamidazole (LAMZ). LAMZ is capable of stimulating the growth of muscle cells and bone-forming cells—or osteoblasts—while suppressing the growth of bone-resorbing cells, osteoclasts.
When LAMZ was administrated to mice orally, it was successfully transmitted into the blood, with no obvious side effects.
“LAMZ-treated mice exhibited larger muscle fiber width, greater maximal muscle strength, a higher rate of bone formation and lower bone resorption activity,” said lead author Takehito Ono.
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 expression of downstream molecules that are involved in the maintenance of muscle and bone.
“Both oral and subcutaneous administration of the drug improved the muscle and bone of mice with locomotor frailty,” said senior author Tomoki Nakashima. “Taken together, the findings show that LAMZ represents a potential therapeutic method for the treatment of locomotor frailty by mimicking exercise.”
Information provided by Tokyo Medical and Dental University.