COVID Supper/Breakfast Does control of COVID show us how to remyelinate

C

NDG is on holiday, probably trying to avoid killing herself by hanging from her fingers on some mountain ledge in the backwaters of somewhere. So I fill her slot with some COVID news that could have implications for MS.

The major killer associated with COVID-19 is……….AGE. When I get infected with COVID-19 it is probably time to pop my Clogs, as I have most of the risk factors. ProfG says “Bring it On” but he and MD2 have turned into “stick-boy”.

The new look ProfG

We all know that will time you start to fall apart, bit my bit. It all moves Southwards and stops working. As you age you do not repair and this is part of the problem with MS.

Repair in MS involves clearing up the debris from immune-attack. Doctor Franklinstein from Cambridge and chums stitched an old mouse to a young mouse together and made them share the young mouse’s heart and blood (Yep a yucky experiment). They showed that the young macrophages could repair.

Now before you turn into a vampire and go off sucking Virgin’s (Ask your father) blood, the Boffs at Cambridge also suggested that if you take a diabetes drug called metformin you can turn the macrophages into young macrophages.

Will this work in MS?

I don’t know, but I do know that there are plans to test this in trials in MS. Are they going ahead. I don’t know as COVID-19 has stemmed MS research.

Now if you remeber we have been saying that the macrophage is probably your first line of defence against SARS-CoV-2. Now here is an hypothesis.

Age is a risk factor for COVID-19 because your macrophages are less effective as anti-viral cells. So old foggies tend to snuff-it but children are often asytomatic, because they deal with it so well.

Now I am not suggesting that you stich yourself to your grand-kids but if the boffs from Cambridge have got the right idea then metformin should protect you from COVID-19.

We know that diabetics have been having a rough time with COVID-19 but there must be enough diabetics taking metformin who get COVID-19.

Is there any data…yes there is

METFORMIN USE IS ASSOCIATED WITH REDUCED MORTALITY IN A DIVERSE POPULATION WITH COVID-19 AND DIABETES.Crouse A, Grimes T, Li P, Might M, Ovalle F, Shalev A.medRxiv. 2020 Jul 31:2020.07.29.20164020. Diabetics are twice as likely to get COVID-19 and are over 3.5 times more likely to die, but if you take metformin your risk of death drops by two thirds (OR 0.33; 95%CI 0.13-0.84)

Metformin and COVID-19: From cellular mechanisms to reduced mortality.Scheen AJ.Diabetes Metab. 2020 Aug 1:S1262-3636(20)30098-7

Type 2 diabetes mellitus (T2DM) is associated with both poorer clinical outcomes during the COVID-19 pandemic and an increased risk of death in such hospitalized patients. While the role of glucose control has been emphasized to improve the prognosis, the impact of different glucose-lowering agents remains largely unknown. Metformin remains the first-line pharmacological choice for the management of hyperglycaemia in T2DM. Because metformin exerts various effects beyond its glucose-lowering action, among which are anti-inflammatory effects. Data from observational retrospective studies that have shown a reduction in mortality in metformin users compared with non-users.

So this bodes well for the MS studies, but I find it hard to believe that there is not enough data in the registries to adddress the effect of metformin on MS…Come on MSBase, MSRegistry and if NARCOMS can’t do this I don’t know who could

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MouseDoctor

26 comments

  • Surely somebody could data trawl to test the hypothesis that Metformin is protective in CoVID? There must be sufficient people with pre-diabetes, diabetes and PCOS taking it. I wonder if young macrophages phagocytose those immortalised EBV infected B cells too?

  • Just as some people with MS are prescribed statins despite trials not yet complete could people with MS not also be prescribed metformin which is an available drug?

    • Yes there are loads…surprisingly it was said that you could tease this data out when neuro doing the proposed study was asked this. We will have something to say on this sometime

  • Mouse,

    Don’t die quite yet as I won’t have anyone to tease.

    Are there any similarities in the mechanisms causing the damage In MS and diabetes? I see that two diabetes drugs have hit the headlines in the recent past – metformin, and pioglitazone.

    With regard to Cambridge, their website states that:

    “CCMR Two: a trial of metformin and clemastine in multiple sclerosis

    The MS Society has agreed to fund a trial of metformin in combination with clemastine, as a potential remyelainting therapy in MS. Unfortuantely, the COVID pandemic has delayed the start of this trial, which we now hope will be before the end of 2020.“

    I like you can’t believe there isn’t some indication that MSers who are also being treated for diabetes are doing better, the same… I don’t know how many MS patients a neuro would see but a proportion will also be treated for diabetes. You’d think an on the ball neuro would have spotted if those treated with a diabetes drug were doing any better (on average).

    I was concerned to hear that MD2 is stick thin. I’ve seen a few photos posted on this site and (pre weight loss) he looked like the love child of Karen Carpenter and Bobby Sands.

  • How can I get prescribed Metformin or at least be involved in a trial?
    From what I have read Metformin mimics fasting and it is fasting that is helping with the remylination? – I’m no good at explaining how & why (probably ms) but I understand when I read about it.
    Anyway I have been fasting and always feel better when I don’t eat!
    I’d absolutely love to be involved in this trial but I don’t have the know how as to go about it! x

    • I was wondering the same thing as well. Perhaps they have made exercise drugable. Exercise the (relative) fountain of youth.

        • If exercise was druggable it would be the most non-compliant drug in existence. Nothing wold even be close. Now if beer and lounging about showed benefit then we would have a blockbuster on our hands.

    • T09-072B
      Caloric restriction enhances astrocytic coverage of synapses and synaptic plasticity in mouse
      hippocampus

      Caloric restriction (CR) has positive effects on brain function and lifespan. A role of astrocytes in these effects is
      still unknown. We performed the study of changes in astrocytes in 4 months old mice after one month of
      calorically restricted diet consisting in 70% calories of ad libitum fed group. CR mice presented a small weight
      loss, while the control group receiving food ad libitum showed a small weight gain. No significant changes in the
      astrocyte density were observed in stratum radiatum of hippocampal CA1 in both groups. Astrocytes were
      recorded in whole-cell voltage-clamp mode for electrophysiological analysis and simultaneously loaded with
      Alexa Fluor 594 for two-photon microscopy morphological study. CR did not produce significant remodeling in
      astrocytic branches resolved with the diffraction limited microscopy. However, estimated volume fraction of
      unresolved presynaptic leaflets was significantly increased after CR. The number of cells coupled through the
      gap-junctions in the astrocytic syncytium was however significantly reduced after CR, but no difference in the
      length constant of coupling was detected. Morphological remodeling was accompanied by activity-dependent
      facilitation of synaptically-induced K+ current and faster K+ clearance in CR astrocytes. The activity-dependent
      facilitation of glutamate transporter current was not different in CR and control mouse astrocytes. However,
      activity-dependent prolongation of transporter current was abolished in CR. These findings suggest that reduced
      glutamate spillover and increased K+ clearance occur due to enhanced astrocytic coverage of synapses in CR
      mice. Next, we performed confocal Ca2+ imaging in astrocytes stained with Oregon Green BAPTA-AM in CA1
      stratum radiatum of hippocampal slices. Spontaneous Ca2+ event size decreased in astrocytic network after CR.
      However, the event duration was increased. Hence, not significant difference was observed in the Ca2+ event
      integral. The long-term potentiation was significantly enhanced in CA1 after CR. We suggest that CR increases
      astrocytic coverage of synapses and promotes synaptic plasticity. These results may explain the effects of CR
      on the brain function.

      Dietary Intake Regulates the Circulating Inflammatory Monocyte Pool

      https://pubmed.ncbi.nlm.nih.gov/31442403/

      Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

      https://pubmed.ncbi.nlm.nih.gov/29874567/

      Intermittent fasting attenuates lipopolysaccharideinduced
      neuroinflammation and memory
      impairment

      https://pubmed.ncbi.nlm.nih.gov/24886300/

      The b-hydroxybutyrate receptor HCA2 activates
      a neuroprotective subset of macrophages

      https://pubmed.ncbi.nlm.nih.gov/24845831/

  • This is really interesting. Is it also how metformin promotes demyelination?

    Love the picture of Prof “Stickboy” G. Hope he’s going to use it as his new profile picture 😬

  • I’m not ready for you to pop your clogs soon either MD – where will this site be without your providing us with wry smiles, chuckles and laugh-out-loud moments!?!

    Surely it’s not so easy to utilise data from those with MS and on metformin, because for example: the number who are Type2 due to reasons such as obesity? ProfG is always emphasising how comorbidities impact on MS and progression. Isn’t it the case the latter will offset the benefits of the former and this is why the trials are needed?

    • At the moment I would suspect it would be without content:-)
      There are people with MS and diabetes and no metfromin and those with metformin. At the end of the day you need a controlled trial. This is on the cards but I wont say more at the moment….

  • That experiment about stitching the mice together must be from 10 years ago?
    It’s one of the few posts I remember most vividly

    You should mark the blog anniversary every year, with special features at the 15 year mark, 20 year mark, etc

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