Ask Barts-MS – April 2018

If you have any questions unrelated to the posts this is the place for you.

Remember when you read the Barts-MS Newsflash on the 1st April 1st that it was an April Fools’ Day Joke.  We don’t think DrK is leaving us. 

FYI. Merck Germany is based in Darmstadt.

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  • My question is what is known about the risks of transitioning to Ocrelizumab from Gilenya. Is a wash out period advisable? if so, have there been instances of disease reactivation during the transition? How far off are Siponimod and the HERV treatment

  • Question: Have you heard of the notion that there is a „permanent threat of PML“ after taking Tysabri while JCV+ and > 20+ Months Treatment duration? If so, would it be advisable to check JCV Titer every 6 Months onwards years later even after having been switched to a new Therapy (Mavenclad)?

  • I have two questions regarding mavenclad.

    1. Are extension studies ongoing and if so when will we have data if there is a sustained effect year 5-6 after treatment start?
    2. After mavenclad treatment do we know anything about what makes the disese ”come back” after part of the immune system is reset? I guess the disese never leaves but i hope you understand my question.

    • In the trial there was 4 year extension data but because Merck terminated the programme in 2011 the long term followo up data will be less complete.

      As for the long term effect, one imagines the regulatory mechanisms win the balance over the disease forming ones but it is only conjecture

  • Is it ok to take rituximab while waiting for ocrelizumab to be available? I have read that there may be a negative reaction because the drugs are so similar.

    • Many patients are on Rituxan and now switch to Ocrevus due to insurance issues. There is no problem at all. IMO the only reason to switch to O. from Rituxan is if you develop antibodies to the drug. Rituxan has a 20 year safety profile.

    • Will people in Great Britain who have paid for rituximab be moved onto Ocrelizumab when it is available?

  • I read with interest Barts' Blog. For a long time now. Disease of any kind is just that. Dis Ease. I appreciate, especially as having a 31 yearl old son with (terminal) (my brackets) GBM grade 4, that all of us want a fix. All of us want it all to be better, to go back to normal.
    But there is no going back. Only forward. And MS, or GBM grade 4 for that matter, is not about going back. Surely it is about transformation. Not just "gettting better", but realising why we have a disease at all.
    It's that realization that is key, in my opionion, not what elstoplasts can help us "manage, cope with" a disease that can transform our lives rather than destroy us.
    All best,
    John-David Biggs

  • Haven't done enough research on it, but is it possible yet (or conceivably possible with some innovation) to analyse a lymphocyte to determine what has activated it? We know many of the pathways that determine when and to what end a white blood cell response is mounted, but for a white blood cell to do something some genomic or other pathway in the cell must be triggered. To find out what is causing MS (and I mean actually get to the root cause of this fascinating disease) you could take lymphocytes from the lesions of recently diseased MS patients and then perform some kind of analysis on them to determine what they have been attacking (or what they have been doing).

    • its been done but 95% of lymphocytes in lesions will be recruited into the lesion due to their surface markers and probably have nothing to contribute to the disease

    • UCL who scheduled and postponed the UCLP MS Research Day three times in 2017 still have the ball in their court. I will chase them up about whether or not they are hosting a research day this year.

    • Turner:
      Sormani MP, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: A meta-analysis. Neurology. 2017 May 30;88(22):2115-2122.

      Lizak N, et al. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017 Mar;88(3):196-203.

      Rashid won (I voted for his choice too).

    • Rashid:"..Contrasting the previous studies,4 our results suggest that disability accumulation in moderately advanced and advanced MS remains substantially driven by inflammatory activity. This hypothesis is supported by the observation that disability trajectories in moderately advanced and advanced relapse-onset MS are modifiable with immunomodulatory therapies. This observation, together with the general concept of the disease trajectory amnesic to the previous disease activity, leads us to conclude that prior disease activity should not preclude ongoing treatment, even when more advanced disability milestones have been reached (such as EDSS step 3, 4, or 6).."

  • Dear prof. G's Team,

    1) What about highly active antiretroviral therapy (HAART)in MS?

    There have already been reports of a very positive response to intensive antiviral treatment (used, for example, in the treatment of HIV like in this case of Julian Gold's patient – – why is not this research continued? Is it because it is unprofitable?

    2) In this ( study, it is written that "In fact, the interest in such trials has almost completely ceased as the introduction and success of immunomodulatory and immunosuppressive therapies for MS.".

    History comes full circle? The association of MS with viruses has been noticed several decades ago, so why antiviral drugs are being tested only recently?
    The current drugs are used without the known cause of the disease (most effective are monoclonal antibodies, which have been used for treating viruses too) so antivirals also could be tested this way, am I right?

    Kindly regards,

  • Why Merck is trying to push Mavenclad to the market regardless of fact, that bioavailability of oral cladribine varies between 37% and 55%, whereas bioavailability of subcutaneous injection (which is relatively cheap) is 100%? [1]

    SCI cladribine could be wonderful treatment option for poorer countries.



    • The bioavailability is 50% so you give twice as much for the same effect.

      we have a paper submitted on this very subject

    • Chris 9.50
      Why Merck pushing Mavenclad

      Because we're a bunch of softies and scared of injections 😉

      And that's what corporations do. Maybe Luis will find us a song about it…..?

    • Mavenclad is a business. Parenteral or injection cladribine is off-patent and won't generate the necessary income required to get Pharma interested.

    • 🙂

      "As the Company’s products lose market exclusivity, the Company generally experiences a significant and rapid loss of sales from those
      The Company depends upon patents to provide it with exclusive marketing rights for its products for some period of time. Loss of patent protection for
      one of the Company’s products typically leads to a significant and rapid loss of sales for that product, as lower priced generic versions of that drug become
      available. In the case of products that contribute significantly to the Company’s sales, the loss of market exclusivity can have a material adverse effect on the
      Company’s business, cash flow, results of operations, financial position and prospects. For example, pursuant
      to an agreement with a generic manufacturer, that manufacturer launched in the United States a generic version of Zetia
      in December 2016. In addition, the
      Company will lose U.S. patent protection for Vytorin
      in April 2017. The Company expects a significant and rapid loss of sales of Zetia
      and Vytorin
      in the United
      States in 2017."

      International sales were $21.3 billion in 2016 , a decline of 3% compared with $22.0 billion in 2015

    • Nice

      "I now realise that you have to work at being ill"

      This is totally me i can relate 1005 with this

      Very well writen


  • A study published online this week in Science provides more support that inhibiting immune metabolism can quell human diseases. Although researchers knew that dimethyl fumarate suppresses immune cells, they weren't sure how. A team led by scientists at Johns Hopkins now reports that the compound cripples an enzyme necessary for glycolysis, bolstering the idea that the pathway can be targeted by drugs.

  • This blog is amazing and thank you Team G/Barts MS for all your hard work. I've said it before but I wanted to say it again. :@)

  • Hi,

    I am going to have a lumbar puncture, is it possible to have the analysis done by Barts? I do not have much trust in the small local laboratories my neurologist supports.
    Who can I contact? Is it possible to send samples from Germany?

  • :O

    NICE says initial 'no' to ocrelizumab for relapsing MS

    The National Institute for Health and Care Excellence (NICE) have provisionally decided not to recommend ocrelizumab for people with relapsing MS on the NHS. This is the first stage of their review process into this new MS treatment.

    Is this a Rituxan call?

  • The brain is not good at repairing itself, but these newly-discovered stem cells suggest there may be a way to improve its ability. These stem cells are in a dormant state, but once awake, they have the ability to generate key brain cells.

    The researchers identified a gene referred to as “tribbles” that selectively regulates G2 quiescent stem cells. The researchers believe that drugs with the potential to target tribbles could be the answer to awakening G2 quiescent stem cells. The next step is to identify potential drug-like molecules that block this gene.

  • What is happening w GNb-AC1? Are they recruiting for PIII? Are they announcing 48wk results at the ANA in April? Do u ave a copy of their webcast March 26/18 calling that can be posted for the rest of us? The webcast March 26/18 is not on Geneuro's website as they promised

  • As a recently diagnoseddiagnosed PPMSler I have a few questions:

    1. Could HSCT be effective for young, not very progressed PPMS patients? If not, what can be done?

    2. Is there any hope for PPMSler for better treatment/stopping progress in the next years(/decades even)?

    • If you can afford it, even if it is considered the most dangerous from all treatment interventions, this is actually the safest there is to halt the disease and only HSCT has shown that good results in PPMS -even if the statistics are worse than in the RRMS group. The earlier the better posibilities.
      Apart from the trial papers you can find online, you can join the HSCT for PPMS fb group.
      The alternative is Ocrevus/Rituxan and off label IV Cladribine. I would try them if HSCT wouldn't work.

  • hi I know this is a bit of a wide ranging question but someone with progressive MS in a wheelchair with deteriorating upper mobility which off label drug would you consider worthwhile? Clad, methotrexate, mitoxantrone, rituximab

  • Please can Barts MS define what 'early relapsing MS' means?
    Is it up to a certain level of EDSS and within a certain amount of years since definite MS or CIS diagnosis? Thanks

  • Survey on Patients experience with Ocrevus

    Half of the respondents reported no improvements, while the other half felt Ocrevus was effective. Thirty-six percent who reported improvements said they could walk better, 36 percent said they were less fatigued, and 14 percent said they could see better. Many respondents reported better balance, bowel movements, and heat tolerance, and less brain fog and numbness.

    Forty-four percent of respondents reported no long-lasting adverse effects. But 21 percent reported more fatigue, 12 percent more pain, 10 percent more itching, and 6 percent more infections after treatment.

  • Must-read blogpost from Wheelchair Kamikaze

    As WK says, "the job of drug company executives is NOT to produce drugs that offer the best result for the patients who take them (like, say, cures). Instead, providing the best outcome for the companies’ stockholders – in the form of ever-increasing profits and ever appreciating stock prices – is the mandated responsibility of these executives"

    So any cure will come only from doctors and academics: that means all of you Prof G, Doc K, the Mouse Doctors, the rest of Team G, and other similar teams around the world.
    Your goals are different from those of the pharma companies, even if many individual executives are on your side

    • Re: ""the job of drug company executives is NOT to produce drugs that offer the best result for the patients …"

      This is not true. I am working with two Pharma companies on a possible EBV vaccine as a MS preventive strategy. Pharma know all about creative destruction; they all want to be ahead of the curve otherwise they will not exist in the future.

    • Vaccinating the whole planet is a more profitable business than targeting the 8-10 million who actually get sick (even if their drugs cost much more than the vaccine).
      Life long treatments is the second best.

  • I have just watched that living proof documentary by Matt Embry. Pharma does not get a good press and neither do the MS charities. He has a very prominent neurologist from Oxford supporting his case against pharma – George Embra. CCSVI was also talked about and doctors who were getting good results from it were told to stop doing it unless they wanted to be stuck off. An interesting watch

    • I think you mean George Ebers, who seems to have saved his criticisms until he was safely retired. Also, his comments pertain to the CRAB drugs not to the more effective current DMTs.
      As I'm sure you are aware, there have been a number of trials to investigate CCSVI liberation therapy, including one by the Zamboni group, the original proponent. All have reported that the procedure has no value.

  • Hi. 7 months post alemtuzumab. My lymph count is 1.2. My child has chicken pox. Do i need to take precautions? Ive already chicken pox as a child.

    • Unfortunately, we can't give personal medical advice on this blog. But in general people with lymphocyte counts >1.0 are immune competent and can deal with infections. People who have immunity to chickenpox don't get recurrent chickenpox.

    • May I please add that it is pertinent as someone who's had chickenpox to be alert for shingles. I received my second dose of Alemtuzumab in Nov and 6 weeks ago developed a rash. Stupidly, for reasons too long too go into, I didn't go to the GP until the Friday. He informed me I was out of the ideal 72 hour window for the antivirals to work. The rash is still going strong and the pain has been horrendous. Consequently I'm now on Gabapentin.
      My advice is don't simply think of the ITP or 'monitor' the rash as I agreed with my ms nurse I would, get yourself to the GP immediately if a rash appears!

    • Thanks FI. Your absolutrly right. You should always over react for any symptoms after a powerful drug which effectively kills your immune system for months. More than ample time for any disease to take root and kill. Luckily my childs rash is mild. Ive not had any rash yet. I asked my neuro and he didn't really share my concerns.

  • In the US, your taxes fund academic research at public universities. Why then do you need to pay expensive, for-profit journals for the results of that research?


    • Interesting but she has missed the point and is living in a dream world, She is is having ago at the academic press and paying subscription based journals.

      She suggests we should have open access.

      However, we now have the open access journal…and the paying journals are doing open access for a cost. They say thanks very much as we have given them an extra income stream and they have all created an open access sister journal. So as they reject you from the high impact print journal they offer access to the open access journal at $3000 a pop.

      However, she is full of it, because open access has just created a new market and you still have to pay to publish. It costs to have open access. It is is only the reader doesnt pay.

      It has spawned hundreds and hundreds of rubbish journals, full of often rubbish papers. They have become so desperate for content that they litter our emails with requests for papers, wasting hours of peoples times deleting emails.

      They could get rid of this in one easy swoop e.g. have a real open access journal…e.g. the Journal of British Research. Have them centrally funded by the UK government where all papers are published, you could have grade 1,2,3,4, etc to give indication of quality.

      However, tell people not to publish in Nature, Science and Cell at £5,000 a pop for open access and the Universities will chastise you if you publish your best stuff in Plos One.

  • Just reading about the EBV and cancers. Have you guys come across patients who have had both Hodgkin lymphoma and MS

  • In Australia, the Pharmaceutical Benefits Advisory Committee (PBAC) announced at 4pm today (20/4/18), they have not recommended the listing of MAVENCLAD® (cladribine tablets) for relapsing remitting MS (RRMS) on the Pharmaceutical Benefits Scheme (PBS).

    The PBAC said that it, “did not recommend the listing of cladribine for the treatment of relapsing remitting multiple sclerosis (RRMS), on the basis of uncertainty in the non-inferior efficacy claim of cladribine versus fingolimod over two and four years.”, pp4-5

    Apparently it will be available to purchase privately but will have to wait to see what the price will be.

  • MRI technique detects spinal cord changes in MS patients

    They applied a technique called BOLD contrast imaging, which detects signal fluctuations based on the magnetic properties of blood hemoglobin as it transports oxygen to the brain and spinal cord, to study the "resting" spinal cord, when the brain has not tasked it to move the legs, for example.
    The study showed that the 7-tesla technique could pick up slight differences in functional connectivity in the spinal cords of 22 patients with a relapsing-remitting form of MS compared to healthy controls. Differences were most pronounced in regions of patients' spinal cords that had visible lesions.
    These findings suggest that the technique might be used to determine whether medications, physical therapy or other interventions are preserving neurological function and thus slowing the course of the disease.

  • If a person with MS has indicators of potential hyperthyroidism (on blood tests, high end of normal range or just into abnormal range), when considering a second line, or first line DMT's and Alemtuzumab would an idea to consider other DMT's first?
    As Graves disease can be a side effect of Alemtuzumab. thanks.

  • AAN 2018

    Non-myeloablative hematopoietic stem cell transplantation (HSCT) is superior to disease modifying drug (DMD) treatment in highly active Relapsing Remitting Multiple Sclerosis (RRMS): interim results of the Multiple Sclerosis International Stem cell Transplant (MIST) Randomized Trial

  • Within a month we have a study on EBV and genes, an anti-HERV trial that was positive, antiretrovirals that could act on both these, a study that connects a leaky gut and its bacteria to a.i. and now… sheeps. I mean c'mon.
    Still, the oddest is that MD posted on T cells.

  • Hi, Have you heard of or know of any research into the use of intralipids in MS? It can be used in fertility treatment to suppress Natural Killer Cells and so seems to have an an effect on the immune system. When Googling, I came across some comments that it has been used in MS patients but couldn't find anything solid. I was just wondering if it could have a double benefit for women with MS who also have fertility issues? Would appreciate your opinion! TIA!

  • having completed two courses of alemtuzumab in 2013 and 2014 I have now been diagnosed with overactive thyroid. Having been prescribed carbimazole I have also been given propranolol to calm my heart. Is the latter ok when you suffer from Ms?

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