A week too late to be the first, but more info on metformin and the remyelination story

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Last week we had the suggestion that metforin can act as an anti-aging agent to make oligogendrocyte precursor cells to promote remyelination.

This wasn’t the first time it had been suggested and it clearly was not the last. So this new study claims to be the first study to show metformin-induced AMPK ,could potentially accelerate regeneration . What a difference a week makes, becuase first becomes second, but in realitity its third or more for example. I say just do some reading. I hate “we are the first ” thing in papers.

It should be banned. As soon as I read this, I start searching and it brings out the worse in me, when I find other peoples work is being ignored.

You have to ask “Do you do your lab work, as good as your literature reviews?”. I recently wrote this in a review,, not realising that the review was supposed to be open access. I said I didn’t want to embarrass the author in public but they asked me to re-write the review to be less contensious…I withdrew my review. I couldn’t be bothered to waste my time on the guff being written. Another recent example also made me search and it turned out the authors were guilty of plaguarism….If the editors have any spine to confront this then this is rather bad news for these people.

Anyway now I have that off my chest, I suspect a lot of you have been contemplating taking metformin. This paper will feed into this. What’s is the evidence in the registries about what metformin does to MS? A trial will need to be done, but will it be one or three trials because it seems that every one is having the same idea at the same time. I guess we will have to wait and see.

AMP-Activated Protein Kinase Signaling Protects Oligodendrocytes that Restore Central Nervous System Functions in an Experimental Autoimmune Encephalomyelitis Model https://doi.org/10.1016/j.ajpath.2013.04.030

PURPOSE: Oligodendrocytes (OLGs) damage and myelin distraction is considered as a critical step in many neurological disorders especially multiple sclerosis (MS). Cuprizone (cup) animal model of MS targets OLGs degeneration and frequently used to the mechanistic understanding of de- and remyelination. The aim of this study was exploring the effects of metformin on the OLGs regeneration, myelin repair and profile of neurotrophic factors in the mice brain after cup-induced acute demyelination.

METHODS:Mice (C57BL/6 J) were fed with chow containing 0.2% cup for 5 weeks to induce specific OLGs degeneration and acute demyelination. Next, the cup was withdrawn to allow one-week recovery (spontaneous remyelination). At the end of this period, mature OLGs markers, myelin-associated neurite outgrowth inhibitor protein A (NogoA), premature specific OLGs transcription factor (Olig2), anti-apoptosis marker (survivin), neurotrophic factors, and AMPK activation were monitored in the presence or absence of metformin (50 mg/kg body weight/day) in the corpus callosum (CC).

RESULTS:Our finding indicated that consumption of metformin during the recovery period potentially induced an active form of AMPK (p-AMPK) and promoted repopulation of mature OLGs (MOG+ cells, MBP+ cells) in CC through up-regulation of BDNF, CNTF, and NGF as well as down-regulation of NogoA and recruitment of Olig2+ precursor cells.

CONCLUSIONS:This study for the first time reveals that metformin-induced AMPK, a master regulator of energy homeostasis, activation following toxic demyelination could potentially accelerate regeneration and supports spontaneous demyelination. These findings suggest the development of new therapeutic strategies based on AMPK activation for MS in the near future. Graphical abstract An overview of the possible molecular mechanisms of action of metformin-mediated remyelination.

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MouseDoctor

12 comments

  • MD what’s you gut feeling, does this work? These trials will never get through to the end. No pharma is going to do a trial to prove a med worth few pence is postive. After spending millions on the trail! Same reason clemastine, asprin went no where. As a leading ms scientist you must have a informed opinion.

    • I am sure if we look hard enough data can be obtained to get a clue. In a US hospital 7 percent of their patients had type 2 diabetes, many will get Metformin I am sure the results aren’t meraculous.

      I already have heard of a number of planned studies,

      • Thanks MD. I agree nothing in the drug world will be miraculous but even it has 10-20% in terms of remylination may just be a enough for MS people to have a normal life. Is there any light at the end of the tunnel. Any idea if anti lingo may show a positive effect to warrant a phase 3 trial? All the papers/experts were saying Ms could be stopped in 10 years. Not sure why.

  • Hi all, I’m interested in any trials you feel worth doing. I have MS and feel there’s got to be something out there (not medical so apologies for the lack of scientific speak) & have a gut feeling (yeah it’s over sensitive to everything, even posts about MS, trials and cures. Please let me know if there’s a register for someone like me ready to assist and desperate not to live my old age with the debilitating time clock ticking?

    • Hi Jane and everyone

      I don’t wait for trials they take to long, instead I read the articles (I’m very scientifically literate) and if it sounds good, is safe, not too expensive, easy to access and I can convince my doctors to prescribe it I can be my own crash test dummy.

      Consequently I started taking Minocycline and Simvastatin years before they were officially approved for MS because I felt the initial published results supported their use. I hav Secondary Progressive MS, my RR disease stated in 1985 and became SP i about 1997, I’ve taken most of the available drugs (Betaferon 1b, Avonex, Copaxone, Mitaxantrone etc) since diagnosis but each became less effective over time so I’m on nothing high level any more except for Baclofen, Minocycline and Simvastatin plus lots of Vitamins/minerals Oh and Metformin now.

      The latter caused some stomach rumbling and mild diahorea but othervise OK and thet settled down after a week or so, fingers crossed it starts some remyelonation where required and I see some results in my next annual MRI, my neurologist signed the prescription and that’s rare for him given I’m always bombarding him with requests for new drugs that sound promising. 🙂

      • Thanks for this but neither minocycline nor Simvastatin are approved for MS. The metformin is the rejuveniatory therapy but it may need a remyelinator. How many Turkeys do you think you have picked

        • I believe science isn’t about accuracy (?) so can let some typos go by but is this article for real?
          It reads like nothing more than a piece to dissuade your readers from looking any further into metformin which appears to have been studied in Peru University and Argentina for its good effects on ms for a good few years.
          I’ll be getting hold of metformin on the internet I didn’t want to get a generic version but, after being signed yp to the much spoken of CU trial nothing more seems to have happened and needs must.

          • “Dissuade the readers” Not at all. So you have heard about the CU plans and I have heard of other plans…I suspect COVID puts this on hold, however te question is metformin or metforin plus

        • They are in Australia, its very unusual for us to be before the US. I found the basic research for both of them years ago and they were compelling. Sometimes we need to take a leap before the authorities, If it’s potentially efficacious and safe then rather than waiting (and I have been since my first symptoms emerged in 1985) so you can’t accuse me of lack of patience, something is required to curb the relentless march of M.S.

          I don’t have the luxury of waiting for things to be approved by your authorities and what I’ve been doing have been working for me, I’ve been stable in a crap kind of way since 2003 since I went to Germany for stem cell treatment (my bone marrow). That may have been a placebo but at least it wouldn’t do me harm. It was less drastic than killing off my whole immune system prior to the SC administration, but I have been relatively unmedicated since aside from the Minocycline, Simvastatin and most recently Metformin. The first two drugs I have been using for over 20 years so the recent addition was not entering my system in short succession to the others.

          If you were in the same position for yourself would you be prepared to wait over 35 years till others gave you permission to do something? I don’t believe I have taken any excessive, non science based risks with my health and neither do my treating doctors.

          • You give us courage to keep going, you don’t need to defend yourself, you are fighting for your life, MS sucks. I do question the long term use of minocycline for MS. Minocin could do more harm, thus if no benefit why continue drug. I have atleast 4 people in my family with MS, including my Mother, Brother, a female cousin and I. My cousin started with Optic Neuritis at 30 vs my direct family started with feet discomfort with NO Optic neuritis. Strange how MS presents differently could be one of the main clues, females are affected greater by Optic neuritis vs men. Could hormonal differences or higher stress levels or women read more than men creating eye strain/stress be clues to the MS pandora box. I am throwing darts at the dart board, seems like that is all we are doing. We need a Serendipity MS moment, the odds are someone will accidentally find the magic bullet or the magic something. Or is MS a black hole of greed , thus no clear path in sight, seems we keep chasing our tails.

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