Lifechanging new compounds are “exercise in a bottle”

Exercise is widely known for its myriad health benefits, and now, researchers are exploring the potential of a pill to emulate some of those advantages.

Recent findings suggest that certain compounds may replicate the physiological effects of exercise, offering promise for treating conditions like muscle atrophy, heart failure, and neurodegenerative diseases.

Presenting their work at the spring meeting of the American Chemical Society (ACS), Bahaa Elgendy, the principal investigator of the project and a professor of anesthesiology at Washington University School of Medicine in St. Louis, highlights the significance of this research. He emphasizes, "We cannot replace exercise; exercise is important on all levels... But there are so many cases in which a substitute is needed."

The focus of the study revolves around the metabolic and growth enhancements that exercise instigates in muscle cells, along with its ability to improve muscle performance.

Elgendy and his team aim to mimic these effects through drug intervention, particularly targeting muscle atrophy and weakness associated with aging, cancer, genetic conditions, or other factors that hinder physical activity.

Key to this endeavor are estrogen-related receptors (ERRs), proteins that initiate metabolic changes during exercise. Over a decade of research, Elgendy's team developed a compound named SLU-PP-332, which activates all three forms of ERRs, including the critical ERRα.

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In experiments with mice, this compound displayed promising results, increasing fatigue-resistant muscle fiber and enhancing endurance during exercise.

To enhance the effectiveness of SLU-PP-332, researchers designed new molecules, optimizing their interaction with ERRs for a more robust response. Comparing the potency of SLU-PP-332 with these new compounds, researchers observed a greater increase in gene expression, suggesting a more potent simulation of exercise effects.

Further studies indicate the potential of ERR-targeting compounds in combating specific diseases such as obesity, heart failure, and age-related decline in kidney function.

Additionally, ERR activity shows promise in mitigating brain damage in neurodegenerative conditions like Alzheimer's disease, although SLU-PP-332 cannot penetrate the blood-brain barrier.

Looking ahead, Elgendy and his team plan to test these new compounds in animal models through Pelagos Pharmaceuticals, a startup they co-founded. They also aim to explore the compounds' potential for treating neurodegenerative disorders, underscoring the broad therapeutic implications of this research.

The research was supported by the National Institute on Aging of the National Institutes of Health under Award Numbers R21AG065657 and RF1AG077160.

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