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  • All the posts on CCSVI, EBV, microbiome, vitamin D, etc. etc., sometimes MS research feels like Dodge City. Is Wyatt Earp in the wings to provide law and order?

  • Having looked at the website (above), I agree that the research of Prof Pender et all looks very encouraging! Something like the Charcot Project perhaps ….comments awaited from our Profs G.

  • Silver fillings/Amalgum fillings (may be they are 50% mercury?) could these be another risk factor to add to the mix? Alongside low vit D. I have quite a few amalgum fillings from when I was in my middle school years. But removing them can release more mercury I understand.

    • I changed my dentist after he ripped me off changing my fillings. Another money making unproven science that has been going around for years. Where does it all end?

    • I would like to be tested for my mercury level. Dentists have this done due to their job handling amalgum. They have it done by nail clippings or hair sample I think. I am going to ask my neurologist if I can get tested, if it comes to it I don't mind paying.

    • Dear anonymous: don't be fooled by the classic charlatan's trick: giving a provocation agent prior to mercury testing and then comparing your results to norms where a provocation agent was not used.

  • I agree on the teeth thing but there to may young people getting ms that haven't got mercury or root canals, look up root canals too

  • Is there any part of the brain that never suffers from lesions? Has there been a comparison study of MRI scans?

  • Am I correct in saying that due to standards of hygiene improving in Western countries the number of cases of glandular fever is expected to rise. This is because fewer children are being exposed to EBV which means they are more likely to develop the infection in early adulthood?

    • Maybe the link is this one the one above does not work for me

      White matter injury: Ischemic and nonischemic
      Robert Fern, Carlos Matute and Peter K. Stys

      Ischemic pathologies of white matter (WM) include a large proportion of stroke and developmental lesions while multiple sclerosis (MS) is the archetype nonischemic pathology. Growing evidence suggests other important diseases including neurodegenerative and psychiatric disorders also involve a significant WM component. Axonal, oligodendroglial, and astroglial damage proceed via distinct mechanisms in ischemic WM and these mechanisms evolve dramatically with maturation. Axons may pass through four developmental stages where the pattern of membrane protein expression influences how the structure responds to ischemia; WM astrocytes pass through at least two and differ significantly in their ischemia tolerance from grey matter astrocytes; oligodendroglia pass through at least three, with the highly ischemia intolerant pre-oligodendrocyte (pre-Oli) stage linking the less sensitive precursor and mature phenotypes. Neurotransmitters play a central role in WM pathology at all ages. Glutamate excitotoxicity in WM has both necrotic and apoptotic components; the latter mediated by intracellular pathways which differ between receptor types. ATP excitotoxicity may be largely mediated by the P2X7 receptor and also has both necrotic and apoptotic components. Interplay between microglia and other cell types is a critical element in the injury process. A growing appreciation of the significance of WM injury for nonischemic neurological disorders is currently stimulating research into mechanisms; with curious similarities being found with those operating during ischemia. A good example is traumatic brain injury, where axonal pathology can proceed via almost identical pathways to those described during acute ischemia.

      This is a review article and we tend not to report on review articles which are typically opinion pieces

  • Is there a reason why stress or stress management is not on the An Holistic Approach to Managing MS slide? As stress increases inflammation.

  • Here's a question for all involved in MS, researchers and patients, (or for any sufferers of incurable diseases); is the lack of money the reason why diseases such as MS have not been cured? If unlimited resources were available for MS research could a cure be found? With all the fund raising and awareness for diseases such as: MS, Alzheimers, ALS, Parkinson's and other neurodegenerative diseases, it seems that no amount of funding would guarantee a cure. If finding a cure is dependent solely on resources then that is a sad state of affairs. It would be difficult to tell a patient suffering from ALS that a cure could be found but society does not want to fund the research that is needed.

    • How many diseases have pharma cured…very few… they manage them

      How many diseases have pharma created…a few……people didn't realise some were diseases until there was a drug for the disease they didn't know they had.

      Does money lead to a cure…no but it will certainly help and without it the cure is less likely to happen…..

      How much cash did Mad Cow disease get?…a lot.
      How many did it treat an cure …I suspect 0…
      How many people with nVCJD about 177 in the UK how many with MS 100,000 and 6,000 a year and how much government cash goes on MS research…very little

      Problem the advisors to government suggest big science that often benefits themselves some of it is not money well spent.

      However with an endless pot of cash I could give you loads of potential fixes..some ideas would be turkeys though

    • Recently there has been a social media explosion in raising awareness for ALS in the states called the "ice water challenge". Lots of celebrities, politicians and company fat cats are dumping buckets of ice water over their heads with the hope that awareness and donations will lead to breakthroughs in ALS research. It will be interesting to see what the outcome will be. It would be nice is some of the billionaires would donate millions to research instead of dumping water on themselves.

  • Why there is still no LSD in MS trials?!
    Or possible they can synthesise a bunch of a brand new drugs, even psychedelic properties of which would demand research by they own 😉

    Serotonin 5-HT2A Receptor Activation Blocks TNF-α Mediated Inflammation In Vivo

    Effects of 5-HT2A receptor stimulation and blocking on immune response.

    Serotonin 5-hydroxytryptamine(2A) receptor activation suppresses tumor necrosis factor-alpha-induced inflammation with extraordinary potency.

    • "Why there is still no LSD in MS trials?"..Because it's an Illegal drug that's why

      As to blocking TNF..this is intentionally done at our peril because this is known to make MS worse

      A first point of call could be to as what happens to MS when you take SSRI serotonin re-uptake inhibitors which have the effect of stimulating the 5-HT receptors

    • Hi Prof Mouse,
      yes, I know about TNF inhibitors and MS, but probably they are non-selective and this is the problem?
      And some papers suggests, that when you target only TNFR1 and spare TNFR2 (as thought how 5-ht2a activation works), this may not be the case, if I got them right

      On SSRI I suppose nobody studied this? And also the effect may be not so pronounced with endogenous ligand (which is expected, nobody trip balls on SSRI's also, but do that on psych. compounds targeting 5-ht2a receptor; although they have seen potent anti inflammatory response with DOI in dosage 20 times lower than is needed to achieve even a very mild trip, strange).

      TNF signaling inhibition in the CNS: implications for normal brain function and neurodegenerative disease.

      Wishing Away Inflammation? New Links between Serotonin and TNF Signaling

      A TNF Receptor 2 Selective Agonist Rescues Human Neurons from Oxidative Stress-Induced Cell Death

      TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.
      A TNF Receptor 2 Selective Agonist Rescues Human Neurons from Oxidative Stress-Induced Cell Death

      TNF alpha promotes proliferation of oligodendrocyte progenitors and remyelination.

  • Dear Prof G, I have been discussing pseudo relapses (relapse with infection at same time) and true relapses that are triggered by infection with my family. I am due to go on my first DMT BG12 end of Oct. I have asked my MS nurse about going on an injectable until then, waiting for a response.

    It seems the line is blurred of what a pseudo relapse is and a true relapse (triggered by an infection). Some time ago I had pulsating in my ear, this turned into a vibration, GP said possibly fluid on ear. I then got a hemi-facial spasm not long after. It began sometime between 4 days and 8 days later (will ask my GP for date). I was not offered antibiotics by the GP and my websearch says fluid on the ear is most likely Otitis media (infection in the ear). So I am unsure if this was a pseudo relapse or relapse triggered by infection. It seems my pseudo relapses have done lasting damage on other occasions. So I wonder why pseudo relapses are not recognised as a relapse ?

  • An MS neurologist said to me earlier this year my relapse was on a natural course. I don't know about this may be I misunderstood what he meant. I get the feeling my relapses are all triggered by something and are not on a natural course. Triggered by asymptomatic infections 30%, triggered by symptomatic infections 60 %, triggered by stress 10%. May be I am stating the obvious. I'm due to go on my first DMT soon.

  • All cancers & autoimmune diseases that are connected with EBV and HERV are found in places with high appearance of dendritic cells. Melanocytes in the skin are dendritic cells, (-> skin cancer), lymph nodes have large amounts of follicular dendritic cells (-> lymphoma), whose cell markers btw are CD21&CD35, the EBV receptors.
    The list goes on (intestine, nasopharynx etc.) You also find them around the BBB.

    I suggest most of the tumors and disruptions of the BBB (same mechanism for Morbus Crohn) result from (maybe specific) HERV activation in dendritic cells through exogenous viruses such as EBV or HSV etc.

  • Team G,

    When will the LAQ Arpeggio P2 and the other P3 start? Since Prof. G already informed us that you are a involved in the coming LAQ clinical trials in PMS, and the patent application is now available, I guess recruitment is about to start shortly?



    Read more: http://www.faqs.org/patents/app/20140235670#ixzz3BCjSXINb

    Can we expect off-label use in case the P2 data is good?

  • I recently came across a presentation on YouTube that Prof G delivered at the MS Society. I was particularly interested in the treatment summary (around 26 mins) Your own diagram shows BMT/HSCT as the most effective treatment (and highest risk) yet you don't mention it in your talk and rarely give it any blog space.
    Is there a reason for this? On one of the few posts discussing this you mention the risk of death being at about 1%, which isn't that different to Natalizumab in risk but is more effective, You talk about patient choice but don't tslk/offer this treatment even thogh potentially it is the best treatment? Can you explain why?

    • Re. BMT and why we don't offer it at our centre

      Unless a therapy is licensed and approved by NICE it is difficult to get the NHS to pay for the therapy. For individual patients you can make a request via an IFR (individual funding request) for the NHS to pay for the treatment. However, if more than 5 patients are likely to meet the criteria in the country then NHS England are likely to reject the IFR and ask you to apply for funding via a business case. The business case is unlikely to get approved as we now have licensed disease modifying therapies that are probably in the same zone of efficacy as BMT, i.e. natalizumab and alemtuzumab. So how do we get BMT licensed as a treatment for MS? You have to do two large phase 3 studies to assess the risk:benefit and then apply to the EMA for a license. The problem with the latter is that the costs associated with this are extortionate and academia or the NHS are unlikely to pursue this. Therefore BMT remains an exploratory treatment in the UK and needs to be done as part of a controlled trials. We have been referring some of our patients with highly-active disease to Imperial College for their stem cell trial that is a form of BMT.

      I am not sure if this helps answer the question.

      In summary, now that we have alemtuzumab licensed as a treatment for active MS I think it is difficult to justify BMT as a treatment for MS. BMT is simply too risky and is not licensed.

    • Thank you for your response. I think my concern with both the drugs mentioned above is they don't stop (or have yet to be proved) progression to SPMS, where as there is data available down on BMT/HSCT patients that have been treated 10/15 years ago and are still in remission. So as you have said before, aren't these drugs just a sticky plaster for MS, yet BMT looks to be longer term remission?
      Isn't Sheffield part of the MIST trial being run out of Chicago?
      Can you elaborate more on how both alemtuzamb and natalizumab have the same efficacy as HSCT?

    • Re: "Can you elaborate more on how both alemtuzamb and natalizumab have the same efficacy as HSCT?"

      It based on "normalising" or bringing brain atrophy rates into the normal range after the 1st year of treatment. At present there are only 3 treatments that do this: (1) BMT, (2) Natalizumab and (3) Alemtuzumab.

      The long-term remission data on Alemtuzumab is not dissimilar to that from the BMT series.

  • Prof G – you often mention brain atrophy in your comments Does this include spinal damage as well?
    Also – to be clear,are you saying that Alemtuzumab and Natalizumab prevent progression to SPMS like HSCT has shown? If you could answer these 2 questions I think it would provide much clarity on people who are considering their next treatments. Because if the drugs are only going to give me 5/10 years then I start to deteriorate with SPMS then HSCT is the best option?

    • Re: "you often mention brain atrophy in your comments Does this include spinal damage as well? "

      No spinal MRI was not done in these studies; but presumably if these drugs are delaying or slowing brain atrophy then they will do the same at the spinal level.

    • Re: "Also – to be clear,are you saying that Alemtuzumab and Natalizumab prevent progression to SPMS like HSCT has shown?"

      To be honest we don't have long enough follow-up on any treatment to be confident of this. But yes, I am saying that it is beginning to appear thay way. Please read the following posts:



    • Interesting, prevent and delay are not the same thing. I read your post on Natalizumab Vs Alemtuzamab, how you were trying to explain to patients their best options. If Alemtuzamab does stop progression to SPMS I am sure that the majority of your patients would opt for it.
      So you have referred patients for Stem Cells treatment even though the medical science behind its benefits is limited at best, but won't refer people for HSCT (chemo + their own stem cells) even though there is much more medical evidence to support it? If you Google HSCT for Multiple Sclerosis you find 100's of papers that support it and plenty of articles that state "it is too risky" but will/might/doesn't work. The argument to the NHS is surely – 1 treatment, potential cure (HSCT) Vs costly DMT's for a number of years? Surely the cost stands up.
      I also find it interesting that you often focus on the effects on the brain, but rarely on the loss of function in arms/legs. If you asked patients what their concern was, I believe the lost of limb function is as much of a concern that loss of brain function,

    • Prof G has referred them to Imperial which is running a stem cell trial- the STREAMS trial. It is not an accepted treatment yet. He's not sending people out for dodgy stem cell treatments abroad

    • I thought it was the Chemo in HSCT that rids the body of MS, returning your own stem sells to you is just to kick start your immune system? Isn't HSCT used to treat certain cancers?
      Re the post above.The dodgy stem cells abroad, agreed anyone that is going to have stem cell treatment abroad that doesn't involve Chemo is going for a purely unproven treatment – which is what the trial at Imperial is at the moment.
      I find it odd that the Professor himself in the above mentioned YouTube video has HSCT as the most effective treatment, but the NHS is the problem.

      FYI – if anyone wants to watch this video on youtube the link is below.

    • You guys are all missing the point. BMT is a stem cell therapy. If it is autologous BMT you get your own stem cells. If it allogeneic you get the stem cells from an HLA unmatched donor. If it is syngeneic you get the stem cells from an identical twin. What does differ in the BMT field is the intensity of the conditioning regimen; it can be very powerful i.e. myeloablative or less powerful and non-myeloablative. Please note that a lot of BMT conditioning protocols used Campath-1h or alemtuzumab.

    • HSCT looks very effective based on the evidence, but the risks are very high and it is hard to justify HSCT now that we have alemtuzumab and natalizumab. I know my colleagues with more experience with BMT will disagree with me, which is why a large number of centres across the world offer this treatment. In the UK I am aware of only two centres; Imperial and Nottingham.

    • I find this interesting that you yourself Professor feel this treatment is very effective but because it is not offered in the UK you don't consider it for your patients. and give it very little air time on your blog. I don't understand why a) most neurologists including my own don't acknowledge this treatment is the most successful for long term remission in MS.
      Would you agree with the below summaries?
      Natalizumab 0.5% chance of getting PML (current 50% chance of death if contracted – and high degree of likelihood of causing serious disability – not proven to stop RRMS progression to SPMS. 50% relapse reduction?
      Alemtuzamab – 1% chance of ITP, 30/50% chance of Thyroid issues. Not long/enough data to confirm if stops progression to SPMS, but data is now indicating that it look as if it delays the onset of SPMS. (60% of patients go into remission after 2 doses)
      Autologous non-myleobative HSCT (Chemo + your own stem cells back) 1% chance of death – long recovery time (6 months +) high risk of infection requiring immediate hospitalization post treatment. But shown to be 70/80% effective in putting RRMS into remission and data now showing this treatment does delay progression to SPMS (though limited patient data available)
      Also fair to say that all treatments work best if RRMS treated early?

  • Isn't secondary autoimmunity the main problem with Alemtuzumab? I know BMT has its own risks, but they seem to be related to aggressive pre-treatment. Would doing MMT after alemtuzumab treatment in place of usual chemo protocols alleviate some (if not all) of the side effects of each treatment alone? Of course, the cost may be prohibitive, but does it make sense otherwise?

  • What about Ocrelizumab/rituximab: do you think effectiveness will be in the same league as Alemtuzumab?

    Should I continue with 6-monthly rituximab or think of switching to alemtuzumab or something else?

    • Re: "What about Ocrelizumab/rituximab: do you think effectiveness will be in the same league as Alemtuzumab?"

      We don't know they have never been compared head-2-head and we don't have phase 3 data available. As rituximab/ocrelizumab are B cell depleting agents there will definitely be safety concerns about switching to alemtuzumab. We need to wait for the phase 3 results of ocrelizumab to get and idea of it risks and benefits.

  • Have you read 'the shameful story of rituximab in MS'?. It's on the web. Rituximab's patent runs out soon, so maybe that's one of the reasons ocrelizumab has been developed. Ocrelizumab's trial into the treatment of rheumatoid arthritis was ended early due to patient deaths. How safe is it?

    • you are correct ocreluzimab is being developed because of patent issues..as to safety they will probably be similar in the long run.

  • Dr G – interested in your further thoughts on HSCT. Are you saying you would offer this treatment if you weren't restricted by the NHS, or would you (as now) only offer drugs as the treatment option?
    More and more MS'ers are starting to talk about this treatment.

    • It looks like Dr Burt is running a HSCT trial for RR patients who have failed first line treatments. Sheffield have signed up to it from what I've read and the trial is recruiting now. Info is on the MS Connection blog site.

    • Re: "Do migraine and all the other mimics cause MRI lesions?"

      Any vascular pathology can cause white matter lesions on MRI. Their distribution, shape and other characteristics are different. The problem is that migraine is so common that the conditions can coexist. You therefore have to rely on a good history, neurological examination, spinal fluid analysis and evoked potentials to help sort out the conditions. Neurologists are quite good at getting the diagnosis of MS correct; they only get it wrong in 1 in 20 cases or less.

  • Since CCSVI is now accepted as a dead end in MS pathology can the blog post a monthly update on stem cell therapies for MS? Patients seem to have much more interest in this rapidly developing area.

    • We post stem cells stuff as they are published, however if people reading these posts start to misbehave just as people commenting on CCSVI did, thenyou can have a once a month post. we turn comments off and do not comment on the papers as it is a no-win situation.

    • CCSVI is not dead yet; there are still some very important studies that have yet to report. We need to be patient.

    • David Wrait (who's an old friend of ours is giving us a seminar at the end of this month. Will try to find paper to establish what they've found but we've been working in the same area for many years (re-establishment of immune tolerance).

    • OK. First impression is that this is a little overhyped by Bristol's PR department!
      Tolerance re-induction is not a new concept (it's been around for 30 years or so, we have quite a few years experience in the field.
      The study uses transgenic mice, where the antigen responded to is known so the re-establishment of tolerance is relatively easy. The paper describes a method of escalating dose induction by subcutaneous injection (as seen in allergy treatment) which is pretty novel.
      However, in MS, the antigens responded to are not known (bizarre as it may seem after all these thousands of man-years of study) so exactly how this will translate to the clinical situation is unclear to me. Indeed one study using subcutaneous injection of antigen ended in disaster, with severe relapses being triggered in MSers and the abandonment of the trial although this study is using much lower doses.
      We'll have to see what happens if/when this approach is tried in MSers.

    • I wish the MS societies would stop to declare each and every new fad a 'breakthrough'!

      For an MSer it is extremely annoying and feels being wind up!

    • I think you should qualify what you men by 'MS Societies' – the MS Society in the UK bases any announcements on evidence based information. So far, they haven't reported on the Bristol findings.

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