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Atherosclerosis is the number one killer in the world, and science is working on solutions to combat this age-related disease. A new mouse study has shown that the drug trodusquemine can melt away the accumulated arterial plaques that lead to heart attacks and strokes.

What is Atherosclerosis?

Atherosclerosis is an age-related disease in which toxic, oxidized cholesterol deposits in the bloodstream produce inflammation in arterial walls. This causes macrophages to swarm to these fatty deposits to clear up this toxic waste.

Unfortunately, our macrophages are not as robust as we would like them to be, and over time, they gobble up so much waste that they either die immediately or become senescent and turn into foam cells.

Foam cells are dysfunctional macrophages that increase inflammation and have become embedded in arterial walls. This rising inflammation works like an alarm system and summons more macrophages to the injury site, and they also succumb to the same fate over time.

Another problem is that, as we age, the immune system declines, and, again, this causes macrophages to increasingly become dysfunctional and stop working properly. They increasingly favor an inflammatory behavior over a healing one.

Ultimately, this build-up of dead and dying macrophages is the basis of the plaques that lead to atherosclerosis. They build up and eventually rupture, causing clots to break off, which leads to heart attacks and strokes.

All humans have some level of atherosclerosis, regardless of lifestyle and diet. As you age, you start to develop fatty deposits inside your arteries. If you live long enough, these deposits will become a problem.

The research

A research team from the University of Aberdeen showed that a single dose of trodusquemine was able to completely reverse the effects of the disease in just a single dose in mouse models of heart disease[1].

In the mouse study, model mice with atherosclerosis had less plaque in their arteries when they had regular doses of trodusquemine or just a single dose. The drug works by blocking an enzyme called tyrosine-protein phosphatase non-receptor type 1  (PTP1B), which is normally elevated in people with obesity, diabetes and inflammatory conditions, such as sepsis, allergic lung inflammation, and diabetic foot ulcers.

The researchers discovered that blocking PTP1B also stimulated the protein AMP-activated protein kinase (AMPK). This is one of the central regulators of cellular and organismal metabolism in cells, and it is activated when intracellular ATP (cell energy) lowers.

AMPK plays key roles in regulating growth and reprogramming metabolism, and it is connected to cellular processes such as autophagy and cell polarity (like a cellular program which determines cell behavior). AMPK stimulation is also similar to the effects of exercise and reduces chronic inflammation.

Trodusquemine is already in trials

Trodusquemine is currently in phase 1 trials for breast cancer, but this is the first time the drug has been tested in animal models of atherosclerosis. So far, the results have been quite impressive and showed that a single dose of the drug appears to completely reverse the effects of atherosclerosis.

The next step will be to move to human clinical trials to see if this drug can improve patient outcome in humans with atherosclerosis. Given that a number of other phase 1 trials for trodusquemine have been conducted, this may contribute to supporting evidence of safety and potentially speed up the process.

The study shows that it not only reverses atherosclerosis but can also reduce the build-up of the fatty deposits that lead to the formation of plaques. If the same effects are observed in human trials, this could mean the drug could be an effective preventative as well as a treatment for atherosclerosis.

Conclusion

The approach here appears to slow the pace at which macrophages arrive at the injury site only to be overwhelmed and contributing to the very plaques they are trying to remove. The researchers here demonstrate that by blocking PTP1B, they can reduce inflammation and block the signals that summon more macrophages to the injury site.

This has the effect of breaking the vicious cycle of inflammation, macrophage arrival, and macrophage death enough to allow natural mechanisms to reduce the plaques already in situ. This has the effect of reversing the development of atherosclerosis.

The damage repair approach to aging makes removing these accumulated plaques one of the key things we need to do in order to combat age-related diseases. For example, SENS aims to find bacterial enzymes capable of digesting these fatty deposits, and these enzymes can then form the basis for drug development. Other groups are testing adjusting macrophage behavior so that they facilitate healing rather than inflammation.

The bottom line here is that all these techniques are viable, and each is a potential path to achieving the goal of removing plaques. Ultimately, it is irrelevant which approach is used to do this; the only thing that matters here is that it works. The end result is what is important, not how it’s achieved. The usual caveats apply here; this is a mouse trial, and we will need to see if the results translate during clinical trials. If they do, then this could be a solution to the biggest killer disease in the world.

Finally, if you are reading this and are interested in being included in future clinical trials please visit the government portal for clinical trials periodically to see if there are trials in your area. 

Literature

[1] Thompson, D., Morrice, N., Grant, L., Le Sommer, S., Lees, E. K., Mody, N., … & Delibegovic, M. (2017). Pharmacological inhibition of protein tyrosine phosphatase 1B protects against atherosclerotic plaque formation in the LDLR−/− mouse model of atherosclerosis. Clinical Science, 131(20), 2489-2501.

About the author

Steve Hill

As a scientific writer and a devoted advocate of healthy longevity and the technologies to promote them, Steve has provided the community with hundreds of educational articles, interviews, and podcasts, helping the general public to better understand aging and the means to modify its dynamics. His materials can be found at H+ Magazine, Longevity reporter, Psychology Today and Singularity Weblog. He is a co-author of the book “Aging Prevention for All” – a guide for the general public exploring evidence-based means to extend healthy life (in press).
  1. November 9, 2017

    If I was one of the (breast cancer) phase 1 trial participants, I’d get a cardiac CT scan or MRI of the major arteries. The results possibly could indicate whether I was getting the real thing (trodusquemine) or the placebo. The [continued] presence of arterial plaque would not be conclusive, but an observed reduction in plaque definitely would, and we would get a preliminary positive indication of efficacy.

  2. January 24, 2018

    I have the same heart disease discribed above. How do I find out about trails for trodusquemine? Please send me any information to

    Logandelworth@yahoo.com

  3. January 30, 2018

    I have blocked arteries (3) could you give me any information regarding human trials of trodusquemine , I am 50 yrs old and I’m looking for an alternative to bypass surgery

    • March 7, 2018

      Alan, have you come across any further information regarding this drug? I’m also very interested in human trials. If you’ve come across anything could you please email me at

      Mike
      Propbalance@att.net

  4. February 27, 2018

    I am interested to take part in any trials for trodusquemine as I have
    blocked arteries in my legs,
    could you send me any
    information please.

    • mm
      February 28, 2018

      Hi Gail, we are not involved in organizing clinical trials we just report on the progress in the field. To find out what trials are happening and which ones are enrolling visit https://clinicaltrials.gov/

  5. March 7, 2018

    Anybody have any info regarding human trials with this drug? Please email me at:

    Mike
    Propbalance@att.net

  6. March 10, 2018

    Please send me infomation
    about Trodusquemine as I
    suffer with blocked arteries in my legs.

  7. March 10, 2018

    Please send me information
    About Trodusquemine I
    have blocked aeteries in my legs

  8. April 7, 2018

    Please advise of your resources for this article. There were a nimber of other similar articles published in Nov 2017 but all my research has been fruitless in finding any information on clinical trials and/or who is currently conducting them. These types of articles create a lot of hope for people and they should be provided with contact and referral information to learn more.

    • mm
      April 7, 2018

      Hi Leslie, this article is a commentary on a mouse experiment which we link to and cite at page bottom. It is certainly not our intention to create hype but rather to report on some interesting research that we hope could lead to a solution to heart disease.

      For details on possible clinical trials please visit https://www.clinicaltrials.gov/

      • June 1, 2018

        More interesting is how the mice specimens develop their atherosclerosis for the study. Often lab animals are given mycotoxins to cause the disease to be treated and studied. Which means they have a cause of heart disease.

  9. May 9, 2018

    TRODUSQUEMİNE Tip 2 diyabet için ilâç olarak kullanılıyorsa piyasada neden yok. Kâlp damarımda 2 adet stent takılı, daha tıkalı damarlarımda var, ateroskloroz için nereden temin edebilirim?

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