Will a sugar diet sort out progressive MS.

W

This week media stories have surfaced that a diet of plant sugar will deal with progressive MS because it rejuvenates the microglia to clear nerve debris away to promote recovery. Great we say. This study identifies a trigger factor called ATG7 . The Autophagy related 7 protein acts as an essential protein for cell degradation and its recycling. But we know this already based on loads of studies from Cambridge and we say NSS.

The Cambrdige diet to rejuvenate the microglia involves the use of metforin and I say watch this space for trials, but should we be comparing with the Stockholm diet of Trehalose (a sugar containing two glucose molecules) that acts on ATG7 to rejuvenate the microglia. Loss of ATG7 in Fruit flies and Mice is related to nerve loss so stimulation of the pathway may save nerves.

Is this what could occur in progressive MS, maybe but the experiment are most relevant to how you recover form a relapse. As ProfG suggested it indicates that mocroglial can be good guys.

Trehalose is only 50% as sweet as table sugar, and does not increase blood sugar or levels nearly as much as the same dose of regular sugar. Side Effects include bloating and diarrhea. Decreasing dosage will prevent these discomforts. 

Berglund et al. Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation, Science Immunology  16 Oct 2020:Vol. 5, Issue 52, eabb5077.

Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery from CNS inflammation in a murine model of MS is dependent on the ability of microglia to clear tissue debris. Microglia-specific deletion of the autophagy regulator Atg7, but not the canonical macroautophagy protein Ulk1, led to increased intracellular accumulation of phagocytosed myelin and progressive MS-like disease. This impairment correlated with a microglial phenotype previously associated with neurodegenerative pathologies. Moreover, Atg7-deficient microglia showed notable transcriptional and functional similarities to microglia from aged wild-type mice that were also unable to clear myelin and recover from disease. In contrast, induction of autophagy in aged mice using the disaccharide trehalose found in plants and fungi led to functional myelin clearance and disease remission. Our results demonstrate that a noncanonical form of autophagy in microglia is responsible for myelin degradation and clearance leading to recovery from MS-like disease and that boosting this process has a therapeutic potential for age-related neuroinflammatory conditions.

.

About the author

MouseDoctor

22 comments

  • They added 5% to the mice drinking water. Does anybody have an idea how to translate this approximately to a dosage for humans? Would this still be a reasonable dosage?

    • I think the mechanism being proposed is different this sugar apparently acts on the myelinating cells the other the microglia

  • Okay. Why is it anything that is discovered. Barts been their and done it but nothing became of it. Yet when another research clinic doee it becomes world breaking news? Dare I say it Barts partiality been bought by the highest pharma bidder? My point is whats the point of any study if its just going to sit on your self as a journal for kudos?

    • Barts been there done that….I am not sure what you are talking about. If you read the comments there were people seeing the media reports (in fact I now realise it was you (IP address the same) who brought this up and were asking should I take trehalose? (In fact it was you who asked this question). You can now read the comments above and below and you can see already that people will be contemplating taking this.Indeed some will do it I am sure. Therefore, I decided to comment on this.

      Did I say it is wrong No, I didnt. Indeed I said the ACtg7 knockout mice get neurodegeneration so stimulation should be neuroprotective. However I said the model where they were doing the study was more similar to recovery from relapsing MS than progressive MS….they treated the mice before they even got disease and it didnt stop the mice getting attack, but they recovered better.

      The concept of microglia and aging was not our work and we never said it was. We gave some credit to Cambridge, but last week ProfG asked the question is blocking microglia a good thing? He argued that microglia have positive roles. This paper supports that view.

      Nothing became of it…..What?….I spoke of metforin trials and I know of three that are planned and would have no doubt started if it was not for COVID-19. Will it go anywhere, unless pharma are involved history has shown us otherwise. Siponimod has now been approaved for progressive MS. Can you ethically deny people access to this agent. Therefore progressive MS trials are going to get complicated and expensive.

      A trial of trehalose. I suspect you can ask…have the Swedes planned this. It is a logical question. What is the safety of trehalose? As it is a glucose will it make you pile on the pounds https://pubmed.ncbi.nlm.nih.gov/12065209/

      Lastly “Dare I say…Barts bought by pharma”…No you may not say!…This is being offensive and uncalled for Anon. I could say “Dare I say you are being an ****-hole…but I won’t say cos I am not that rude.;-).

      • Thanks MD for your detailed and clear answer. Not having a go at personal level. Problem with MS research is clear. Nothing gets to phase 3 that stops pharma gravy trian. Examples clementine, Lipoic acid, asprin, etc. Anything that is cheap and already available unless its funded by charity. Such as MS society. As for being a*rsh*le, damn right. Integrity is something you earn constantly and is not just a badge or label you wear because you did some good in the past. I see so many leads and papers on this blog that go nowhere including those by barts. Because as you state unless pharma does something. This is the heart of the problem. Heres a idea. Why doesn’t Bart put a case together for a possible cure for MS and say it will cost 100 million to do a 3 phase trial and crowd fund it. I bet you my last dollar you will get all the money you need. Instead pushing old drugs for other forms of ms to placate pharma. And I will be very surprised if barts shrugged its shoulders say we have no idea how to cure ms.

        • The sucess in MS has created a problem. Pharma are creating drugs for pwMS, but the academics have made pharma jum through hurdles and now pharma cn say academics have to work to the same standards. As it getting the drug approved after two successful trials cost millions…academics can never achieve this….so maybe academics need to think what devil they are creating. Clemastine and lipoic acid will be in phase II/III as soon as covid-19 allows..

          Leads that go nowhere including Barts..maybe fair point but you have to understand that we do not have the pocket money to do the next stage studies without support, if the support does not come then there is no study.

          Why doesn’t Bart put a case together for a possible cure for MS and say it will cost 100 million to do a 3 phase trial and crowd fund it. I bet you my last dollar you will get all the money you need…….I dont believe this for a minute…money does not growon trees. The MS Society has this vision. Have they got the £100,000,000 yet……No

          Instead pushing old drugs for other forms of MS to placate pharma…. Eh. Have you moved from Sidcup.

          Shrugging shoulders..we have plenty of ideas thanks

          • Heres what’s been over looked. MS is a disease of the rich. Those affected are still mainly from Western rich countries. If someone told you if you are affilicted (God forbid) with MS we have a cure and you can live normal life why wouldn’t you fund it? If normal people can spend 50000 to go to Russia why wouldn’t they spend that money at a cure gamble. I myself was going to pay 80000 to London Bridge for HSCT until I thought Alemtiuzumab was better. Remember turkeys will not vote for Christmas. Besides isn’t this the real purpose of this blog to get international audience to create another fund raising arm? Besides what do you have to lose? Not sure who is from siddcup? But if someone gets under your skin then he or she is pricking a open wound. I’m just telling it like I see it and not stating their facts but trying to create debate and new line of thought. Wouldn’t you do the same if you had MS and wanted to be cured? Put your big boy pants on say as follows. “We are dogs bollocks in MS research and have possible, gives us 100000000 to fund you sl*gs if you want to be cured.” Let me start the ball rolling i will give 1000 if though it was likey to work.

          • The problem with the cure is you think it is until you show it is not….We cna cure mice..can we do it in humans (I will submit the first paper shortly)

    • I’ve been hesitating to point out the same thing, while not to the whole Barts team, but to one particilar professor. BartsMS Blog has been the best place for me to gather professional filtered research updates, but I really cannot ignore and appreciate this almost sour grape tune. MS patients could benefit from having a sense of security, while it may not be sustained in the long run but there is nothing better they can do – lower stress is correlated with better prognosis?

      MD’s comments are mostly objective, and trustworthy. But contents from others can be highly subjective, and even inconsistent. I understand at the end of the day, this is Bart’s own blog, not 100% targeted at MS patients, or at least the rose tinted odometer should work in a way really warn patients you should take a grain of salt to the content or head out, but I guess for some of us we will get our heads in anyway?

    • Problem is if you take it the digestive system will break it down or use it for the kerbs cycle to make energy. Plus Jo guarantee it will get to the nervous system.

      • Intermittent fasting seems like an obvious and easy “tool” for PWMS to use. Do you think 16/8 is effective? I am assuming black coffee and sparkling no-calorie flavored water is ok during fasting hours?

  • Autophagy Promotes Oligodendrocyte Survival and Function following Dysmyelination in a Long-Lived Myelin Mutant

    Abstract

    The Long–Evans shaker (les) rat has a mutation in myelin basic protein that results in severe CNS dysmyelination and subsequent demyelination during development. During this time, les oligodendrocytes accumulate cytoplasmic vesicles, including lysosomes and membrane-bound organelles. However, the mechanism and functional relevance behind these oligodendrocyte abnormalities in les have not been investigated. Using high-magnification electron microscopy, we identified the accumulations in les oligodendrocytes as early and late autophagosomes. Additionally, immunohistochemistry and Western blots showed an increase in autophagy markers in les. However, autophagy did not precede the death of les oligodendrocytes. Instead, upregulating autophagy promoted membrane extensions in les oligodendrocytes in vitro. Furthermore, upregulating autophagy in les rats via intermittent fasting increased the proportion of myelinated axons as well as myelin sheath thickness in les and control rats. Overall, this study provides insight into the abnormalities described in les as well as identifying a novel mechanism that promotes the survival and function of oligodendrocytes.

    Here, we have shown that intermittent fasting can upregulate autophagy in oligodendrocytes and increase myelination in les as well as control CNS. Interestingly, disruptions in oligodendrocyte protein homeostasis have been described in several CNS myelin disorders, including vanishing white matter disease (van der Voorn et al., 2005; van Kollenburg et al., 2006), multiple sclerosis (Getts et al., 2008), and Pelizeaus-Merzbacher disease (Dhaunchak and Nave, 2007). Moreover, autophagy can be easily enhanced through diet or pharmacologically with drugs, such as rapamycin (Menzies and Rubinsztein, 2010). Therefore, further investigation of this pathway may lead to novel therapies that aid in the survival and function of myelinating cells in certain myelin diseases.

    One more reason to fastng

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4128639/

  • I don’t know much about this stuff… Will human gut enzymes just break trehalose down into not-helpful glucose? Or does taking this by mouth as part of diet get trehalose into the CNS? (I do understand that trehalose is not yet convincingly proven to be helpful– my questions are based on the speculation of what if it turns out to be so.)

By MouseDoctor

Translate

Categories

Recent Posts

Recent Comments

Archives