A groundbreaking study has uncovered fresh compounds that could serve as exercise pills to emulate physical exercise’s positive effects.
Various substances such as creatine, beta-alanine, and caffeine have garnered attention for their purported ability to enhance exercise performance and aid in recovery. While these supplements may offer some advantages, it’s essential to recognize that they cannot fully substitute for the comprehensive health benefits derived from regular exercise.
However, imagine if there were an exercise pill that could replicate some of the benefits of physical activity. Scientists in the United States have been exploring this intriguing concept, aiming to condense certain health advantages of exercise into a convenient, swallowable form.
In recent research, scientists have made significant strides toward creating a drug capable of replicating some of the cellular benefits of exercise. Although still in its early stages of development, the novel drug has shown promising results in initial tests on rodents, demonstrating its ability to activate a natural metabolic pathway typically induced by physical activity.
When administered to mice on a daily basis, the drug, known as SLU-PP-332, appears to enhance muscle function, fitness levels, and endurance, all without requiring the animals to engage in increased physical activity.
According to a press release from the American Chemical Society, early trials of SLU-PP-332 indicate that it may effectively simulate the physical advantages of exercise.
The objective is to develop a drug that activates specific cellular mechanisms in humans typically triggered by exercise. These mechanisms play crucial roles in preserving and rejuvenating muscle mass, as well as boosting the functioning of cellular powerhouses, explained Bahaa Elgendy, the principal investigator and an associate professor of medicinal chemistry and anesthesiology at Washington University School of Medicine in St. Louis.
Elgendy emphasized the irreplaceable importance of exercise on multiple fronts, stating, “We cannot replace exercise; exercise is important on all levels.” However, he noted that there are numerous scenarios where an alternative is necessary.
Exercise yields comprehensive benefits for both physical and mental well-being. Elgendy and his team aim to replicate its profound physiological effects, particularly its ability to enhance the metabolism and growth of muscle cells, leading to improved muscle performance.
A drug capable of replicating these effects could potentially counteract muscle deterioration and weakness associated with aging, cancer, certain genetic disorders, or other conditions that hinder regular physical activity, as highlighted by Elgendy. Additionally, it might offer a solution to mitigate the side effects of certain medications, such as new weight-loss drugs that lead to the loss of both fat and muscle.
The metabolic changes initiated by exercise begin with the activation of specialized proteins called estrogen-related receptors (ERRs), which exist in three forms: ERRα, ERRβ, and ERRγ. Following approximately a decade of research, Elgendy and his team developed a compound named SLU-PP-332, which activates all three forms, including the most challenging target, ERRα. This particular ERR variant plays a crucial role in regulating exercise-induced stress adaptation and other vital physiological processes in muscle tissue. In experiments conducted on mice, the researchers observed that this compound enhanced a type of muscle fiber resistant to fatigue while also improving the animals’ endurance during treadmill running sessions.
Consequently, the endurance of rodents on treadmills significantly improves with the administration of the drug, enabling them to run 70 percent longer and 45 percent further compared to those not receiving the medication. This enhancement is likely attributed to the skeletal muscle cells’ improved ability to maintain their energy balance.
Subsequent experiments revealed that mice receiving SLU-PP-332 twice daily for a month gained significantly less fat compared to untreated mice, despite consuming the same amount of food and engaging in equivalent levels of exercise as before.
Pharmacist Thomas Burris from UF, at the time of the results’ publication in 2023, explained, “This compound essentially instructs skeletal muscle to undergo the same adaptations observed during endurance training.” He further noted, “Upon treating mice with the drug, we observe a shift in their whole-body metabolism towards utilizing fatty acids, akin to what occurs during fasting or exercise. Consequently, the animals begin to lose weight.”
The team is currently conducting tests on their latest generation of molecules in animals, beginning with studies on mice that exhibit characteristics resembling human conditions such as heart failure, obesity, and kidney dysfunction. Their objective is to determine whether the new compounds could offer therapeutic benefits for these conditions.
Moreover, there is emerging evidence suggesting the relevance of the ERR alpha receptor to Alzheimer’s disease, as its activity has been associated with reduced levels of misfolded proteins in the brain. Elgendy expressed the team’s interest in exploring the potential of treating Alzheimer’s and other neurodegenerative disorders through this avenue.
Elgendy emphasized the pivotal role of ERRs in various health conditions, stating, “In all of these conditions, ERRs play a major role.” He highlighted the potential benefits of effectively activating these receptors with a compound.
However, Elgendy cautioned that despite the promising progress, the compound is not yet a drug and has not undergone human testing. The researchers acknowledge the extensive work required to further test the molecules in animals, understand their metabolism in the body, and make any necessary adjustments before advancing the candidate drugs to human trials. Elgendy underscored the time-consuming nature of this translation process, stating, “Translation takes a lot of time.”