New ‘exercise pill’ could induce fitness benefits without exercise

Scientists in the US claim to have reduced some of the health benefits of exercise to a pill to swallow.

The new drug is in the early stages of development, but in initial experiments with rodents, the drug appears to tap into a natural metabolic pathway triggered by exercise.

When given to mice daily, the drug, called SLU-PP-332, appears to improve muscle function, fitness and endurance, all without requiring the animals to move more than they are used to.

Presenting the latest results at the 2024 spring meeting of the American Chemical Society, principal investigator and chemist Bahaa Elgendy of the University of Washington says he and his team have succeeded where others have failed.

His drug’s metabolic target was once thought to be “undruggable,” or too difficult to trigger with pharmaceuticals. But in the end it may not be so.

If researchers can successfully target the same metabolic pathway in humans, Elgendy believes it “could lead to the development of therapeutics for some of the most challenging diseases we face today, such as neurodegenerative diseases and heart failure.”

For years, scientists around the world have been working to build an “exercise pill” that could deliver at least some of the benefits of exercise to those who need it.

Physical activity taps numerous metabolic pathways that can improve human health in many ways, but one pathway with particularly impressive health benefits triggers estrogen-related receptors (ERRs).

These receptors are found in muscle, heart and brain tissues and are known to regulate a wide range of genes associated with metabolism, immunity, inflammation, homeostasis, development, cell growth and reproduction

However, historically, they have proven to be really difficult to target. Exercise is one of the only ways to get the ERR ball rolling, so to speak.

Scientists from the University of Florida (UF) and Washington University in St. Louis have been working on a version of an ERR drug for a few years. It is designed to drill down into not one but three different types of ERR, a feat that has never been achieved before.

Elgendy and his colleagues are so encouraged by their progress that they have created a start-up pharmaceutical company, called Pelago Pharmaceuticals, which they anticipate will “launch the clinical translatability of this goal.”

In previous experiments, Elgendy and his colleagues have shown that when mice are given SLU-PP-332, it increases a type of fatigue-resistant muscle fiber in their bodies.

This, in turn, improves the rodents’ endurance on treadmills, allowing them to run 70 percent longer and 45 percent longer than those not given the drug. This is probably because their skeletal muscle cells are better able to maintain their energy balance.

Subsequent experiments found that mice that took SLU-PP-332 twice a day for a month gained 10 times less fat than untreated mice, even though they continued to eat the same amount of food and exercise the same amount than before

“This compound basically tells skeletal muscle to make the same changes seen during resistance training,” UF pharmacist Thomas Burris explained when the results were published in 2023.

“When you treat the mice with the drug, you can see that their whole body metabolism switches to using fatty acids, which is very similar to what people use when they fast or exercise. And the animals start to lose weight.”

This does not mean that SLU-PP-332 is a perfect substitute for exercise, but it appears to trigger a molecular pathway that conveys many of the benefits of exercise to the heart, brain, and kidneys.

Some new compounds similar to SLU-PP-332 are even being designed to cross the blood-brain barrier, possibly delivering drugs to the brain that can keep the cells there fighting in shape.

“Many people cannot exercise, and a pill could be very beneficial to mimic or enhance the effects of exercise for people who are aging, for people with certain diseases, or who are dealing with some muscle loss using other medications Elgendy says in a clip from the American Chemical Society meeting on YouTube.

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