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I was interviewed by Medical News Today about a new drug LAMZ. This article was written and published by Medical News Today on September 20th, 2022.
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Physical activity is known to promote bone and muscle health.
Aging, lifestyle, and chronic disease can lead to physical inactivity, which is associated with bone and muscle loss.
New research has now identified a drug that can mimic physical exercise in mice.
The new drug, called locamidazole, can increase bone formation, mineral density, muscle thickness, and muscle strength in mice.
When we are physically active our bones and muscles work together to make them stronger. To maintain bone health, the American College of Sports Medicine recommends a combination of weight-bearing activities 3–5 times per week and resistance exercise 2–3 times a week.
Research has shown lifelong exercise to be beneficial for preserving bone health, and a reduction in physical exercise results in bone loss. The CDC advocates regular physical activity to strengthen and maintain muscle and bone, research has shown improving muscle strength can have a moderate effect in relieving joint pain for people with osteoarthritis.
Despite its benefits, modern-day living is associated with a lack of physical activity. According to the World Health Organization, physical inactivity is a serious but “insufficiently addressed public health problem” with up to 85% of the world’s population leading a sedentary lifestyle.
Inactivity is also associated with an increased risk of chronic disease. The British Heart Foundation attributes more than 5 million deaths worldwide to physical inactivity, which equates to one in nine deaths overall.
Chronic conditions, injury, and aging may mean it is more difficult to undertake physical activity, which can lead to muscle weakening (sarcopenia) and bone loss (osteoporosis).
New research undertaken at Tokyo Medical and Dental University (TMDU) has identified a new drug that can mimic exercise, and promote similar changes in muscle and bone.
The work, led by Professor Tomoki Nakashima, has been published in Bone Research.
Stronger muscles and bones with a pill
In the study, the research team identified a new compound called Locamidazole (LAMZ) as a potential therapeutic drug that can cause similar effects to exercise.
To test the new compound, the researchers administered either 10mg/kg of LAMZ orally once daily, 6mg/kg LAMZ by injection twice daily, or a control solution for 14 days to male mice.
Administration of LAMZ orally and by injection showed changes in both muscle and bone. Researchers noted that the treated mice had wider muscle fibers and increased muscle strength when compared to the non-LAMZ-treated mice.
Endurance was studied using a treadmill device, the LAMZ-treated mice were less fatigued and traveled a longer distance than the non-treated mice.
In an interview with Medical News Today, Dr. Joseph Watso, assistant professor at Florida State University, who was not involved in the study, explained:
“It is thought-provoking that while the changes in distance traveled by the animals were small (around 2%), the increases in adjusted maximal muscle strength and muscle fiber width were quite substantial after 14 days of LAMZ administration.“
How does LAMZ work?
Using gene analysis, the researchers showed that LAMZ increased the number of mitochondria—the powerhouse of the cell—in muscle and bone cells. They noted an increase in the expression of the gene for the PGC-1 alpha, a protein known to maintain muscle and bone cells and increase the production of mitochondria.
“PCG1a is a known transcriptional coactivator that increases mitochondrial biogenesis. This is an interesting feature of the agent they identified as mitochondrial biogenesis is a hallmark physiological adaption of exercise training,” Dr. Watso explained to MNT.
To understand the pathway further, the researchers orally administered LAMZ to mice whilst blocking PGC-1 alpha. They found no increase in muscle strength, indicating the effects of LAMZ on muscle and bone through PGC-1 alpha.
3D images of bone samples generated using Micro-CT showed an increase in bone thickness, density, and bone mineral content, confirming the cell study findings of increased formation and a reduction of bone loss.
“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 study’s lead author Takehito Ono commented.
Exercise or a pill?
The study has shown that LAMZ can reinforce bone and muscle with no negative effects on surrounding tissues, and can function as a therapeutic drug by reinvigorating muscle and bone via PGC- 1α, mimicking physical exercise.
Dr. Watso summarized the findings:
“The article provides convincing evidence in animals for an agent with a high potential to improve bone and muscle health. Like most agents evaluated in animals, the key next question is whether those findings will translate to humans. Of course, without any harmful side effects that may not have been observed in the animal studies.”
He cautioned that “it will be an arduous task to develop one elixir of health to replace the innumerable benefits of regular physical activity and exercise. That said, continued efforts are needed to reduce the incidence of, and burden associated with, preventable diseases.”
In certain cases, medication may be the safer option than exercise, but where possible, “exercise should be the first consideration for those who have the capability to be physically active,” said Dr. Watso.
Despite this, “it is certainly worthwhile to continue to examine population-specific risk factors and pathophysiology for potential treatment targets,” he added.
By Anna Guildford, Ph.D. on September 20, 2022 — Fact checked by Catherine Carver, MPH
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As always, feel free to share your thoughts, comments, and questions.
Thanks for reading.
-Joe