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In a medical facility located in northern Norway, slightly below the Arctic Circle, a significant trial is underway that may revolutionize the way we approach aging in the future. Known as ExPlas, or exercised plasma, this study involves extracting plasma from young and fit individuals who regularly engage in physical activity and administering it to individuals between the ages of 50 and 75 who are in the initial stages of Alzheimer’s disease. This is the first time this method has been tried on humans.

The complete findings will be accessible in 2025 with the aspiration that it will introduce a novel approach to revitalizing the mental and physical well-being of older individuals, and potentially eventually for all individuals who have predominantly sedentary lifestyles.

The medical community has recognized for quite some time that exercise is an incredibly effective form of medicine. Research has shown that physical activity can decrease the likelihood of dementia by as much as 45%, as well as promoting healthy bones, flexible blood vessels, and regenerating muscle fibers.

In August 2023, a recent research published in the British Medical Journal revealed that incorporating just an hour and fifteen minutes of moderate physical activity per week, which is half of the recommended amount, can lower the chances of developing cancer, heart disease, and dying prematurely. Despite the guidance provided by public health officials, a quarter of the population in the UK is still considered inactive. A survey conducted in over 100 countries discovered that nearly a third of individuals engage in minimal to no physical activity.

Is it possible for the pharmaceutical industry to assist with this issue? Researchers in countries such as the UK and Japan have been researching exercise mimetics for several years – medications or injections that could imitate some of the positive impacts of exercise on the body. The evidence shows that we may be making progress towards this goal.

According to Christiane Wrann, an assistant professor of medicine at Harvard Medical School, physical activity results in the release of various hormones into the bloodstream.

Scientists are currently uncertain about which hormones from exercise are the most advantageous, so the ExPlas trial is using a wide-ranging strategy. The trial involves administering blood plasma from individuals who regularly exercise, which is a straightforward method of transferring potentially beneficial hormones to patients. Wrann explains, “The Norwegian concept is to use plasma as the medication and provide it to those in need.”

However, there is also a more targeted approach that is becoming increasingly popular. In 2012, researchers identified a hormone known as irisin, which is produced by muscles during physical activity. This chemical acts as a messenger, communicating with different areas of the body. In November 2023, Wrann and her team showed that irisin is able to reach the brain and remove the harmful amyloid plaques associated with Alzheimer’s disease. This discovery is a significant advancement in understanding the role of exercise in protecting the brain against dementia.

Wrann and colleagues have established a new business called Aevum Therapeutics, with the primary goal of bringing irisin to the market as the first exercise-based remedy. This may be achieved by replicating the hormone through medication, altering genetic makeup to produce more irisin, or directly administering higher doses into the body.

At this point, it is uncertain if this could potentially be a new treatment for Alzheimer’s or simply a medication that is beneficial for overall exercise. Wrann suggests that if irisin is proven to have health advantages in clinical studies, it could pave the way for numerous exercise-related medications.

According to Wrann, there has not been a successful translation of exercise benefits into a drug. However, if it were possible to capture a significant portion of exercise benefits in a medication, it could greatly improve patient outcomes.

Is there a universal pill?

Is it possible for us to no longer have to go to the gym in future Januarys? According to Andrew Budson, a neurology professor at Boston University, this is a convincing idea.

“I believe there is nothing inherently problematic about attempting to mimic the positive physiological effects of exercise,” he states. “I have no objection to that. I personally enjoy exercising and do not plan on giving it up, but on a hectic day, it would be beneficial to have the option of taking a medication instead of missing out on the health advantages of exercise altogether.”

But, according to experts like Wrann, exercise drugs are primarily intended for disabled and elderly individuals who have become immobile due to enforced inactivity, rather than those who are busy or lazy. At the Tokyo Medical and Dental University, researchers are investigating the key component of exercise that helps prevent osteoporosis and sarcopenia (muscle loss and weakness), with the goal of using it to develop a new drug for combating frailty and potentially even restoring mobility.

In the fall of 2022, they revealed a new substance known as locamidazole which activates two body signalling pathways related to exercise and responsible for maintaining muscle and bone health. In experiments with mice, oral supplementation of locamidazole showed promising results in improving muscle size and function, as well as promoting bone growth.

Despite the positive results, scientists are proceeding with caution due to the potential for undesirable or harmful side effects. This has hindered past efforts to treat exercise as a medication.

According to Jonathan Long, a faculty member at Stanford University in California, AMPK (adenosine monophosphate-activated protein kinase) is an enzyme that is activated through physical activity. This activation leads to the removal of excess sugars in the bloodstream, potentially reducing the chances of developing type 2 diabetes. However, the AMPK mechanism is intricate and activating it has a widespread impact on various tissues in the body, not just blood sugar levels.

According to Long, there has been a pursuit to create AMPK activators. A pharmaceutical company was able to achieve this a couple years ago. They administered these molecules to monkeys, resulting in the expected decrease in blood glucose levels. However, the monkeys also experienced dilated cardiomyopathy, a condition where the heart becomes enlarged and poses a threat. As a result, this approach proved to be ineffective.

Antidepressants and fat jabs

The main inquiry being pursued by Long and his colleagues is whether there exists a secure method of artificially triggering the body during periods of inactivity when exercise-related pathways are not anticipated to be active.

According to Wrann, it is improbable that a medicine will be developed that can fully mimic the benefits of exercise for everyone. This is because physical activity plays a role in numerous biological processes, and even if it were possible to target all of them, it would likely not be without risks. Wrann states, “I do not believe it is practical for a single pill to provide the 20 positive effects that exercise has on the body.”

Researchers imagine a potential future in which multiple treatments, all derived from studying exercise and biological pathways, exist for various conditions such as osteoporosis and brain protection. At University College London, Professor Jonathan Roiser is currently conducting a project funded by Wellcome to extensively examine the effects of moderate-intensity exercise on the immune system, metabolism, and their influence on mood and motivation. One potential outcome is the development of a novel category of antidepressants based on exercise.

Long is especially intrigued by the potential for exercise to offer alternative solutions to current obesity medications. In his studies, his team has uncovered a compound known as Lac-Phe (N-lactoyl-phenylalanine) that is produced by the body during intense physical activities like sprinting or strength training. This compound is able to enter the brain through the bloodstream and has been found to decrease feelings of hunger.

Long explains that in ancient times, physical activity often involved fleeing from predators. As a result, the body’s natural response was to decrease digestion and suppress appetite in order to prioritize sending glucose to the muscles for survival during escape.

Lac-Phe could potentially be a useful addition in combatting the current problem of obesity. Although Ozempic and Wegovy have become popular options for weight-loss, Long notes that they have restrictions, such as the need for weekly injections to sustain their effects.

He suggests that there may be potential for finding innovative ways to use Lac-Phe in order to achieve longer-lasting reduction of appetite. It is also possible that Lac-Phe could be formulated into an oral medication rather than requiring injections.

Some people view imitating physical activity as a method of potentially altering the body’s metabolism to improve fat-burning. Research on mice has suggested that increasing irisin levels can transform regular fat cells into brown fat cells that burn energy, resulting in weight loss even when consuming a high-fat diet.

For the last two decades, Ronald Evans, a faculty member at the Salk Institute for Biological Studies in San Diego, California, has been researching a protein known as PPAR-delta (peroxisome proliferator-activated receptor-delta). He refers to this protein as a “master switch” that is triggered by endurance exercise and can be targeted with drugs.

According to research, PPAR-delta can aid in increasing the ratio of slow-twitch muscle fibers and signals the body to switch from burning sugar to fat. After extensive research, Evans is now confident that he has found a drug that can activate this switch; however, he still requires data to prove its safety and effectiveness in humans.

Since large funding organizations are typically doubtful of the concept of exercise drugs, Evans has had to present it as a potential treatment for either fatty liver disease or the genetic muscle weakening disorder Duchenne muscular dystrophy in order to secure regulatory approval and funding for clinical trials.

He expresses a desire for the development of an exercise medication within the next decade. However, the scientific hurdle lies in the fact that all research in the US is funded by the National Institutes of Health. The issue arises when considering prescribing a drug that mimics the benefits of physical activity, as there may be questions about what exactly it is treating when exercise is a viable option.

However, should evidence begin to surface confirming the safety and efficacy of these drugs in human use, it is widely accepted among experts that they have the potential to be highly successful and widely used medications in the future. Long affirms this sentiment, stating, “If we are able to achieve this, I have no doubt that these drugs would be incredibly valuable treatments.”

Source: theguardian.com