New Exercise Pill Promises Fitness Benefits sans Exercise

Researchers in the US purport to have condensed certain health benefits of exercise into an ingestible pill.

Although still in its infancy, this innovative medication has shown promising results in preliminary tests on rodents, harnessing a natural metabolic pathway typically activated by physical activity.

When administered daily to mice, the drug, known as SLU-PP-332, appears to enhance muscle function, fitness, and endurance – all without requiring the animals to increase their usual activity levels.

Presenting the latest findings at the American Chemical Society’s 2024 Spring meeting, lead researcher and chemist Bahaa Elgendy from Washington University asserts that his team has achieved success where others have previously struggled.

Unlocking the Undruggable Metabolic Target

The metabolic target of their drug was previously considered ‘undruggable’, implying it was too complex to stimulate with pharmaceuticals. However, this assumption may no longer hold true.

If researchers can effectively target the same metabolic pathway in humans, Elgendy believes it “could pave the way for the development of therapies for some of the most challenging diseases we are facing today, such as neurodegenerative diseases and heart failure.”

For years, scientists worldwide have endeavored to create an ‘exercise pill’ capable of conveying at least some of the benefits of physical activity to those in need.

Physical activity engages numerous metabolic pathways that can enhance human health in various ways, but one pathway, particularly renowned for its health benefits, involves estrogen-related receptors (ERRs).

Regulating Multifaceted Functions in Muscle, Heart, and Brain Tissues

These receptors are present in muscle, heart, and brain tissues, where they regulate a wide array of genes associated with various functions, including metabolism, immunity, inflammation, homeostasis, development, cellular growth, and reproduction.

However, targeting these receptors has historically proven challenging, with exercise being one of the few effective methods to activate them.

Researchers at the University of Florida (UF) and Washington University in St. Louis have been developing a version of an ERR drug for several years. This drug is designed to target not one but three different types of ERR – a milestone never before achieved.

Encouraged by their progress, Elgendy and his team have established a startup pharmaceutical company, Pelago Pharmaceuticals, with the aim of advancing the clinical applicability of this target.

Enhanced Muscle Endurance

In previous experiments, administration of SLU-PP-332 to mice resulted in an increase in fatigue-resistant muscle fibers in their bodies. Consequently, the endurance of these rodents on treadmills improved, enabling them to run 70 percent longer and 45 percent farther compared to those not receiving the drug. This effect is likely due to enhanced energy balance in their skeletal muscle cells.

Subsequent experiments revealed that mice receiving SLU-PP-332 twice daily for a month gained only one-tenth of the fat gained by untreated mice, despite consuming the same amount of food and engaging in the same level of physical activity as before.

Pharmacist Thomas Burris from UF, during the publication of the results in 2023, clarified that “This compound essentially directs skeletal muscle to undergo the same adjustments seen during endurance training.”

Effects of SLU-PP-332 Treatment on Fatty Acid Utilization and Weight Loss in Mice

“When mice are treated with the drug, their overall metabolism shifts toward using fatty acids, which closely mirrors the metabolic response observed during fasting or exercise. Consequently, the animals begin to lose weight.”

While SLU-PP-332 may not fully replicate the effects of exercise, it appears to activate a molecular pathway that imparts numerous benefits of exercise to the heart, brain, and kidneys.

Researchers are formulating certain newly developed compounds similar to SLU-PP-332 to cross the blood-brain barrier, with the potential to deliver medication to the brain and uphold cellular health.

“Given that many individuals may be unable to engage in exercise, a pill could offer significant advantages by replicating or augmenting the effects of exercise, particularly for aging individuals, those with specific ailments, or individuals experiencing muscle loss due to certain medications,” Elgendy stated during a segment of the American Chemical Society meeting available on YouTube.

Read the original article on: Science Alert

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