You know exercise is good for your health, but life can get in the way of your physical fitness. Perhaps you don’t have as much time to hit the gym as you’d like, or have a medical condition that prevents you from exercising at all. Maybe you hate working out. Wouldn’t it be easier if you could just take a pill to reap the rewards of exercise?
The idea may not be so far-fetched. After testing new drug compounds that appear to mimic the physical benefits of exercise in rodents, scientists say a pill may someday be able to do the same in humans. Bahaa Elgendy, Ph.D., a medicinal chemist and associate professor of anesthesiology at the Washington University School of Medicine in St. Louis, was scheduled to present his team’s findings Monday at the spring meeting of the American Chemical Society (ACS).
As you age, you gradually lose muscle mass, strength, and function—a type of atrophy called sarcopenia. Elgendy’s team hopes an exercise-mimicking pill could treat muscle atrophy and improve the physical fitness of people with serious ailments such as cancer, heart failure, and neurodegenerative diseases, according to an ACS news release.
“We’re not saying by any means or forms that people shouldn’t exercise,” Elgendy tells Fortune ahead of his presentation. “But [the drug] hopefully will help people who cannot exercise. And, in other cases, it can complement exercise programs to give more benefits to patients as well.
“Or, it can be combined with the new wave of drugs: anti-diabetic drugs and drugs that are used for obesity and weight loss.”
Elgendy and his team spent about a decade developing a compound called SLU-PP-332. It activates a group of proteins called estrogen-related receptors—ERRα, ERRβ, and ERRγ—which Elgendy says are “responsible for activating some of the most important metabolic pathways in tissues with high-energy demand.” The most elusive target, ERRα, regulates exercise-induced stress adaptation as well as physiological muscle processes. Mice treated with SLU-PP-332 showed improved endurance running on a rodent treadmill. It also increased a fatigue-resistant muscle fiber in the animals, researchers found.
Next, the team created new, patentable molecules with the goal of making them more safe, potent, and efficacious than SLU-PP-332, Elgendy says. Further study of rat heart cells suggests the new compounds do more strongly mimic the effects of exercise.
“The new generations we developed that I’m going to talk about today, these are predicted to make it hopefully to the clinic one day in the next five years,” Elgendy tells Fortune. “The translation from animals to humans takes a long time. We need to do a lot more preclinical testing, which is vital to ensure safety.”
What are exercise mimetics?
Exercise mimetics are a proposed class of drugs that aim to do exactly what the name suggests: mimic the health benefits of exercise. SLU-PP-332 and the new compounds fall into this category.
“These compounds simulate some of the same adaptations that occur in muscle with exercise. So, your muscles think that they are exercising even though they may not be,” Thomas Burris, Ph.D., chair of the Department of Pharmacodynamics at the University of Florida, tells Fortune. “They improve metabolic health, they cause weight loss, fat mass loss, improved insulin sensitivity, [and] improved exercise endurance.”
Burris is part of Elgendy’s research team. With the skyrocketing popularity of GLP-1 agonists—the class of drugs that treat obesity such as Wegovy and Zepbound—people are increasingly turning to pharmaceuticals to aid in weight loss, Burris says. But he stresses that GLP-1s cause the loss of muscle mass and function in addition to body fat. The exercise mimetics he and his colleagues are studying may temper those effects.
“There’s a great need for something to be used in combination so that people who are losing that weight are primarily losing fat mass and retaining good-quality muscle, because that can lead to future complications,” Burris tells Fortune. “Older people who go on [GLP-1s] who already have maybe some reduced muscle quality, losing that mass could lead to some disabilities.”
Jamie Alan, Pharm.D., an associate professor in the Department of Pharmacology and Toxicology at Michigan State University, wasn’t involved in the research but tells Fortune the results are exciting. She’s intrigued by the team’s plan to focus on the brain in future study.
“These particular drugs that they used in this first go-around, they don’t cross into the brain at all,” Alan says, referring to SLU-PP-332. “[Researchers] said it could potentially have more far-reaching benefits if we design a drug that still hits these receptors but has the ability to get into the brain.” That way, they can study the compounds as possible treatments for neurodegenerative diseases. Previous research has highlighted ERRα as a potential therapeutic target for Alzheimer’s disease.
Ideally, an exercise-mimicking drug would be in the form of a pill people could take once a day, says Burris, who has collaborated with Elgendy for years.
“He’s making the compounds and I’m testing them, and we test them all the way from biochemical methods to the whole animal,” Burris says. “We continually optimize them, trying to make them more drug-like so that they can go into humans hopefully in the not-too-far future.”
For more on the health benefits of exercise:
Subscribe to Well Adjusted, our newsletter full of simple strategies to work smarter and live better, from the Fortune Well team. Sign up for free today.
