Progress to Exercise Mimicking Pill

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Japanese researchers have made progress on an exercise pill. The exercise pill is a drug that mimics the effect of exercise on muscle and bone. They want to provide this for people who are bedridden or otherwise unable to exercise.

LAMZ augments muscle and bone by mimicking calcium signaling to induce PGC-1α. Schematic of LAMZ function in the augmentation of muscle and bone. Exercise increases the calcium concentration in muscle and bone cells, inducing calcium signaling. Under this signaling, PGC-1α and Mef2c are activated and reciprocally drive their expression. Mitochondriogenic, myogenic and osteogenic genes are induced as well, together augmenting the muscle and bone. Thus, LAMZ facilitates the calcium signaling pathway and restores locomotor fitness.

They have established a novel, three–part drug screening system and discovered a locomomimetic drug, LAMZ. LAMZ enhances myogenesis and osteoblastogenesis via stimulation of calcium-PGC-1α signaling. It can be administered by multiple routes and improves both muscle and bone mass, resulting in increased capacity for locomotion. Therefore, LAMZ has potential as a therapeutic drug for patients with impaired locomotion, such as those with sarcopenia and osteoporosis.

Medication is safer than exercise, but there are no drugs that reinforce both muscle and bone when administered alone. Multiple medications increase the risk of adverse events; thus, there is a need for individual drugs targeting both tissues. To this end, we established a novel sequential drug screening system and identified an aminoindazole derivative, locamidazole (LAMZ), which promotes both myogenesis and osteoblastogenesis while suppressing osteoclastogenesis. Administration of this drug enhanced locomotor function, with muscle and bone significantly strengthened. Mechanistically, LAMZ induced Mef2c and PGC-1α in a calcium signaling–dependent manner. As this signaling is activated upon physical exercise, LAMZ mimics physical exercise. Thus, LAMZ is a promising therapeutic drug for locomotor diseases, including sarcopenia and osteoporosis.

Reinforcement of the muscle and bone during exercise coincides with anabolic changes in both muscle and bone (e.g., increase in proliferation and/or differentiation of myocytes and osteoblasts and a decrease of these in osteoclasts). In search of drugs that can be a substitute for exercise, we established a sequential drug screening system, in which the differentiation of three lineages of cells in muscle and bone (myocytes, osteoblasts and osteoclasts) was quantified. First, we developed a novel method for quantifying the proliferation and differentiation of myocytes. Among 296 compounds in a chemical library, eight were found to enhance the proliferation and/or differentiation of C2C12 cells, a myocyte cell line. Compound 17b, an aminoindazole derivative that showed the strongest promotion of myotube formation, enhanced myosin heavy chain expression. This compound increased the expression of Myod1, Myog, Klf5 and Mef2c, transcription factors known to be induced during myogenesis and to increase differentiation

LAMZ ameliorates the frailty of muscle and bone
To determine whether LAMZ has efficacy as a novel therapeutic drug for impaired locomotion, we orally administered the drug to tail suspension model mice, a disuse model associated with unloading, in which both the muscle and bone of the hindlimb become frail.27 Oral administration of LAMZ significantly upregulated Ppargc1a expression in muscle and bone. In mice treated with this drug during tail suspension, there was an increase in the width of the muscle fibers. Micro-CT analysis revealed that LAMZ treatment increased bone mass. A significant increase in osteoblasts and the osteoid surface was observed in these mice. There was no significant difference in the bone formation rate, owing to the increase in bone formation by tail suspension itself. Osteoclastic bone resorption was decreased by LAMZ treatment in these mice. The reduction of the muscle and bone induced by the disuse model was mitigated by LAMZ treatment

13 thoughts on “Progress to Exercise Mimicking Pill”

  2. Going to take a wait-and-see on this. Note the date of the article referenced below. Apparently it worked then, if taken with artificial AMP, but part of the problem I saw at the time was the drug mentioned was only available in small amounts for researchers and to actually buy enough to treat even one human would have exceeded six figures in USD each year, presuming you could even persuade the suppliers to sell it to you without a license.

    From 1st of August 2008, 13:41 GMT:
    Forget About the Gym, Take a Pill
    Drugs could replace exercise altogether
    By Gabriel Gache, Science News Editor

    “Researchers from the Salk Institute for Biological Studies have recently identified two signaling pathways that can be activated through drugs in order to increase endurance. Both pathways are naturally activated through exercise, but the effects of a workout session can be mimicked with the help of drugs, this way helping people unable to move maintain the overall health of the muscle mass.”

    • Sure, but a lot of drugs are insanely expensive when produced in quantities for testing, but much cheaper if mass produced. You should probably expect almost all biologicals to converge on the price of insulin as the market for them gets big enough to justify genetically engineering bacteria to produce them.

      • I agree, mass production (accompanied by demand, of course) is key. One of the reasons that even the people that would appear to be the beneficiaries of massive income inequality will eventually find it working against them is because, if they are the only ones that can afford, say, Colgate or Crest toothpaste, the price would rise to thousands of dollars a tube, or more, as the factories would still need to be built and maintained and operated). Now multiply this by practically everything they touch or use. Eventually most of them could not afford it, and the prices would rise even higher for those who still could until, perhaps, even they could not.

        When I worked with ICBMs there was a very complex mechanical gadget made of carefully machined steel (held the launch code for the keys). Sometimes we would have to remove them from the console and zero out the code for transport (or in certain emergencies that never happened, fortunately). Even in training simulators, we had to be extremely careful with them as they each cost over 100k in 2022 USD. Just a couple of pounds of steel, but an entire factory had once been built to produce only a few thousand of them and they were almost irreplaceable because of this.

        So yes, pharma, as in most other things, mass production (and matching demand) is key . . . as long as the monsters don’t get control of the patent (or all the manufacturing if it is no longer patent protected) and then escalate the price sky-high. This happens quite a bit with mealy mouthed pharma execs whining about how it is their responsibility to maximize profits (and, although they don’t say it, not to maximize human survival).

        Seriously, people that try to make a killing on selling food and water and building supplies after a hurricane can go to jail for blatantly taking advantage of people that have to have those things. How does this not apply to pharmaceuticals taking advantage of people that have to have those things? Reasonable profits are fine, but seriously, all the market will bear?

        • It’s not patent protection that most of the crazy drug pricing is caused by. It’s regulatory limits. eg. the FDA in the USA.
          Your typical drug is only protected by patent for less than 10 years by the time it’s on the market. More like 5-7 years by the time it becomes widely used.

          After that, anyone is allowed to make it under patent law. But the FDA steps in and only gives permission for a limited number of companies to sell it for medical purposes. Often only one.
          That’s what’s going on with these extreme cases where something has been available for generations and then suddenly shoots up in price (eg. insulin or adrenaline injections for allergic shock)

          Somehow, the general ire at such shenanigans has been misdirected at the patent system instead of the real culprit. Suspiciously so.

  4. I’m pretty sure that, while this might get you halfway there, at least some physical motion is going to be required. Muscles gradually lose the capacity to stretch if not stretched, anyone who has had a limb in a cast is very familiar with this.

    • The encouraging thing about this is that muscle growth is normally a cycle of minor damage followed by healing back stronger. And as you get older, the time necessary to recover from that damage gets longer and longer. So you can do less and less exercise, and the net gain from exercise declines.

      With something like this, you could largely get the strength gains without that damage cycle, and limit your exercise to just stretching exercises, which are pretty safe to do every day, indeed need to be done more frequently than your recovery time, to work.

      • I would be very curious to see if stretching would make up the difference with something like this. It seems to me that it could result in increased flexibility without normal effort, which would be great. Perhaps big increases in athleticism would be possible.

  5. We are not going to be fixed by mimmicking exercise, diet and anti aging pills, but by fixing our liver with a proper diet and truly needed supplements that will allow it to do its work.

    • Proper diet is bull, it’s total energy in vs out, Otherwise we’d of started getting obese in the 50’s, when our diet really changed, not the 90’s

      But you know what changed in the 70’s/80’s?

      Air conditioning and sit down jobs became abundant as standing, sweating labor jobs declined.

      That’s what did us in, we don’t expend calories any more.

      • I’m pretty sure that “proper diet” involves stuff like vitamins and minerals and fruit and vegetables and fibre and a lot more things than merely total energy content.
        There is more to health than just bodyweight.

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