Friday, 1 September 2017

Unrelated Comments - September 2017

Sometimes you want to say something unrelated to the thread. This is the place for you.


53 comments:

  1. What is happening to your hand campaign?

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    1. Our #ThinkHand campaign is still very active. We have lots planned for the campaign over the next few months and will keep you updated. The Chariot Trial is one of the proposed outputs of the campaign. The good news is the #ThinkHand surveys that we did last year on this topic have now been published:

      Dubuisson et al. Disease modification in advanced MS: Focus on upper limb function. Mult Scler. 2017 Jun 1:1352458517717811

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  2. Are people with MS more or less likely to feel low after the summer ends?

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    1. I suspect more likely to feel low. MSers are also humans and humans are susceptible to SAD (seasonal affective disorder).

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  3. ProfG had mentioned diet. Can he talk about fasting diet and if it has benefits?

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    1. Will do in my series of diet posts. Intermittent fasting makes a lot of biological sense, but more on that later.

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  4. I am changing subjekt....is LAQ still a futute treatment?

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    1. I am a little more optimistic. Teva need to get it licensed so that we can do add-on studies. The real place for LAQ is as an add-on neuroprotective drug. Let's wait and see what happens with the PPMS trial. We should have the results in the next few months.

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    2. Let's hope the adverse profile that came up with the higher dose won't snowball.

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    3. The real place for LAQ is as an add-on neuroprotective drug

      Will it be Class 1 evidence

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  5. Dear all,

    I will never thank you enough for your blog!

    Two things caught my attention recently. First, an article about the FDA authorizing gene therapy for leukemia: https://www.nytimes.com/2017/08/30/health/gene-therapy-cancer.html?smid=fb-nytimes&smtyp=cur
    The technology seems to be ready to retransplant "corrected" lymphocytes, quite thrilling.

    Second, this is one of the most successful among the many attempts to find a vaccine for an herpes virus. One could have a long debate on the ethic behind this trial but they claim that it was quite conclusive:
    http://nypost.com/2017/08/31/thiel-backed-drug-firm-secretly-tested-herpes-vaccine-overseas-report/
    Would there be a possible use of these research in MS?

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  6. I am a postgrad researcher and I don't know what to do about magpies sealing my research ideas. This has happened to me twice now. Who do I trust and what does your team do about this? Should I keep my mouth shut when people ask me about my MS research?

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    1. Should say 'stealing'.
      There was a article written in the BMJ 1998. A compliment: Having your research ideas stolen.

      At the bottom it mentioned:

      " So the next time that you share an idea with someone and then see it in their grant proposal feel proud: it was an idea good enough to steal. "

      This comment doesn't make me feel any better.

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    2. We've all been there, it doesn't make it any easier to deal with. Short of keeping quiet when asked what you're up to/your ideas until what you've got is published, there really isn't much else you can do.

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    3. Within the group, we work as a group and their is collective benefit
      and would hope that members of the group are not frightened talking about ideas and we do not create a competitive environment.

      People will steal something from us once, as the magpie will be dead to us after that.

      However if you put ideas out-there you have to live with the consequences. We give more ideas away than we can deal with. Why not confront the person and discuss it so the magpie is working for you and you get shared glory. We could have had loads of nature papers, only we didn't do the work. Sometimes people have ideas at the same time.

      Depending on where you are there are some labs that will put more than one person on the same project the one getting the results survives the other sinks.

      There are labs which lock their fridges, incubators so that people don't find out what people are up to.

      A terrible working environment. I guess those stealing your ideas are your work mates or should I say colleagues as they are not on your Christmas list. Expose them for the leeches they are, but best keep you mouth shut about ideas if this is causing recurring thefts.

      However also some people have ideas but are never doers. ProfG throws loads of ideas in the air, we can catch and run with them or drop them. Ask yourself are you a person that acts on your ideas?
      Do you see your ideas throw before testing the next one.

      There are people who will sell their grandma to get ahead.

      In the US there is the office of Science Integrity and their are avenues if the magpies have dogey practises.

      However, if it is outside your environment and you putting ideas out there you have to change your behaviour. We put ideas out there on the blog and have to live with getting there after being pipped to the post.

      Likewise, once you publish the ideas generated are fair game. We have been too slow to exploit some of our own research work and will suffer the consequence

      However, you have ideas so they can be tested and you can't do everything yourself, collaborate.

      We knew cannabinoids must be controlling neurotransmission 2-3 years before the science, nature and Neuron papers by others

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    4. Thanks. I am not in a research group unfortunately, my research area is cross discipline. I'm pretty much on my own.
      I'm keeping a wide birth now from these magpies.

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    5. I believe that ideas, like air and water, belong to no one. As a scientist I am happy if an idea that I convey spreads. So yes glad if someone is "stealing" my ideas. As an MSers I am glad when my comments are answered :). If you are afraid of having the work of a manuscript stolen put it on BioArxiv

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  7. The entry of B-cell therapies is not that new, in fact it has been used for about 10 years with RTX in America, and now Sweden is under trial to finally establish RTX as an option for MS.

    Both share the idea that early introduction to B-cell therapy (high efficacy therapy) could maybe prevent the transition to SPMS (flipping the pyramid of under treatment/over treatment).

    But from what we know till now from case studies, with first-lineres of low efficacy for 10 years and another 10 of RTX (now would be O.) didn't prevent people from transitioning to SPMS, maybe delay(?). So far, noone had RTX for 25 years, so this is just a theory. And of course, B-cell therapies as all do nothing for SPMS.

    Wonder if this theory could have a real base.

    And since there is no good answer on how to prevent SPMS, but only improve the quality of life or RRMS, -which B-cells are really good at-, how can one be against HSCT responsibly.


    PS Also, if you ask me as a patient, my doctor said "everythings gonna be alright" but failed to answer "for how long?" and "by what means?" (by hidding behind the reserve capacities of a young brain is the answer). Doctors don't tell and most patients dont ask, so you have your answer to why "quality of life" answer does not include high efficacy drugs, because "reserve capacities" and ignorance.

    PS2 NEDA does not include cognitive impairment and many more deficits, and the brain atrophy was not that much on the center of research. So, it is not NEDA.

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    1. "plasma cells in the CNS are left unscathed" this anti-CD20 therapy does not address these plasma B-cells, does not cross the BBB and target follicular lymph tissue in the meninges that may be contributing to progressive disease. The poor decrease in disability progression in PPMSers bear this out. This strategy of targeting lymphocytes in the periphery, whether B or T-cells, with monoclonal therapeutics is not adequate for treating progression. When will we acknowledge this? Or do the drug companies dictate the direction of MS therapies irregardless of their efficacy?


      Answer from a user from the blog

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  8. Is it normal to.have alemtuzumab over 4 days from.tuesday to Friday. THEN have the last dose on Monday. Surely your increasinf the risk making antibodies to the drug with 2 day gap. It takes 1 b cell to attach to cd50 then turn to mass produce them as plasma cells. Should I push my care provider for consecutive day treatments?

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  9. What if the oligodendrocytes were regularly renewed (not a static pool). In this case the progressive form of MS could have a simple explanation. Let say MS causes the death of a constant fraction of all oligodendrocytes. In the case where the renewal goes down (aging) or the killed fraction increases (primary progressive) the population of oligodendrocytes would then constantly deceases (despite the renewal). Would it be a credible hypothesis?

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  10. Changing the thread again, sorry XoR.
    A question about Tecfidera , low lymphocyte count and opportunistic (or ordinary) infections. I have asked this before but have not had a reply, apologies for asking again. If the answer is 'that a present we don't know', that is fine.
    Apart from the remote chance of PML are there any other infections that people on DMF with a lymphocyte count 0.6-1.0 are more vulnerable to?
    Are there any precautions that we should be taking? Any additional risk with travelling to countries in Africa and Asia or places with more exotic diseases?

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  11. Its been written on the blog a couple or so times that teriflunomide as second line, or more, is more effective than first line but I can't find anything to back that up. Can some one provide pointers?

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    1. I couldn't find links when I posted the above, here are what I've found now, perhaps because I used Google directly and not the the blog.
      http://multiple-sclerosis-research.blogspot.com/2017/01/thinkspeak-charcotproject-what-i-love.html
      http://multiple-sclerosis-research.blogspot.com/2017/05/clinicspeak-real-world-evidence.html
      http://multiple-sclerosis-research.blogspot.com/2017/06/researchspeak-charcotproject-there-are.html

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    2. The 7 Jan post contains the figure showing relapse rate and disability progression by prior treatment.
      Teriflunomide the dark horse of MS

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    3. Continuing my list of Teriflunomide posts:
      NDG's post with comment from ProfG:
      http://multiple-sclerosis-research.blogspot.com/2017/03/dont-write-off-write-off-reassessment.html

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  12. When is the next MS day? Prof G told me in clinic a few weeks ago that the information will be posted on the blog?

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    1. I have heard today, that UCL have cancelled the research day.

      Hope its not because they don't have any research news worth talking about. Only joking...

      It is sad as BartsMS would be having a bumper year, two drugs that we have been intimately involved with, have now become licensed in 2017.

      We have probably worked out how alemtuzumab works

      We probably worked out why it causes autoimmunity

      We have probably worked out how cladribine works

      We have worked out what the Cambridges have been keeping quiet:-(

      We have are giving all people access to treatment

      We have recruited PROXIMUS

      We have recruited and finished the spasticity trial

      We have worked out how the spasticity drug works

      We have identified new neuroprotective agents

      We have....we have.....much more that you won't get to hear about in this format. Sorry.

      Hoping that we can go to Stornaway or find some new way

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    2. It's a pity that you can't showcase all your work. I found the early research days rather dull overall e.g. a presentation on how trials work etc. Now you've got something interesting to talk about - there's no outlet!

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    3. Such a shame the research day has been cancelled. As an alternative suggestion could people do pieces/lectures to camera instead that we could then watch online? seems such a shame not to hear about all these exciting developments!

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  13. A new paper (September 2017) on HSCT benefits on aggressive MS, from Sweden

    http://jnnp.bmj.com/content/early/2017/09/02/jnnp-2017-316271

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  14. Team G, Do tattoos impact on MS? Perhaps this could be an area for MS research?
    In the past I have heard more than one tattoo (for the general population) is better for the immune system than just one tattoo.
    I ask this as there is a immune reaction when a tattoo is done.
    However, There is new research to say that tattoo ink enters the bloodstream and travels to vital organs. If you have a tattoo you have large and colourful lymph notes apparently (BBC World update: Tattoos the hidden health risks).

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  15. Can't have access to the whole article but this is an abstract on the b-ees and il-s. Curious to read the rest.

    B cell–derived IL-6 initiates spontaneous germinal center formation during systemic autoimmunity

    Abstract

    Recent studies have identified critical roles for B cells in triggering autoimmune germinal centers (GCs) in systemic lupus erythematosus (SLE) and other disorders. The mechanisms whereby B cells facilitate loss of T cell tolerance, however, remain incompletely defined. Activated B cells produce interleukin 6 (IL-6), a proinflammatory cytokine that promotes T follicular helper (TFH) cell differentiation. Although B cell IL-6 production correlates with disease severity in humoral autoimmunity, whether B cell–derived IL-6 is required to trigger autoimmune GCs has not, to our knowledge, been addressed. Here, we report the unexpected finding that a lack of B cell–derived IL-6 abrogates spontaneous GC formation in mouse SLE, resulting in loss of class-switched autoantibodies and protection from systemic autoimmunity. Mechanistically, B cell IL-6 production was enhanced by IFN-γ, consistent with the critical roles for B cell–intrinsic IFN-γ receptor signals in driving autoimmune GC formation. Together, these findings identify a key mechanism whereby B cells drive autoimmunity via local IL-6 production required for TFH differentiation and autoimmune GC formation.

    http://jem.rupress.org/content/early/2017/09/11/jem.20170580

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  16. what are your thoughts on the article in the Daily Mail referring to a man with progressive MS who has been in a wheelchair for 10 years have been given HSCT?

    http://www.dailymail.co.uk/health/article-4891036/Therapy-offer-new-hope-MS-patients.html

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    1. From the article ‘The main aim of this treatment is to halt further damage caused by MS,’ added Dr Kazmi. ‘For those with significant disability, we don’t expect a dramatic transformation.
      ‘If they are in wheelchair, they are likely to stay in one. But they may not get worse.'

      Delete
    2. yes but the point is they are saying they will not get any worse and I believed that people in wheelchairs with progressive MS were not eligible for such treatment!
      for someone in a wheelchair to not get any worse, that is a huge bonus!
      Prof G has the eligibility changed?

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  17. I am curious to know if you would consider tamoxifen for women on ocrevus and have a family history of breast cancer.

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  18. "Researchers identified a Cytokine, called Macrophage migration inhibitory factor (MIF), along with its related protein, D-dopachrome tautomerase (D-DT), which are associated with progressive MS. These cytokines worsen the disease by increasing inflammation within the central nervous system. The researchers also linked enhanced expression of MIF with a gene variant that occurred more frequently in MS patients with progressive disease -- particularly in men."

    The difference in genders, and perhaps this has to do with (or not) hormones, seems to influence even the innate immune response.

    https://www.sciencedaily.com/releases/2017/09/170919164128.htm

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    1. "Researchers identified a Cytokine, called Macrophage migration inhibitory factor (MIF), along with its related protein, D-dopachrome tautomerase (D-DT), which are associated with progressive MS."

      There goes the theory that MS is one disease.

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    2. What a coincidence. I just wanted to ask the same question.
      The publication can be found here:
      http://www.pnas.org/content/early/2017/09/13/1712288114

      Does fhis research advance the notion of the "four subtypes of MS" propagated by Neuopatholgists?

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  19. What a great time to be a... researcher

    A potent and long-lasting gene immunotherapy approach prevents and reverses symptoms of multiple sclerosis in mice, according to a study published September 21st in the journal Molecular Therapy. Multiple sclerosis is an autoimmune disease in which T cells destroy the myelin sheath—the material that surrounds and protects nerve cells in the brain and spinal cord. The researchers used a viral vector to deliver a gene encoding a myelin sheath protein to the liver, thereby inducing robust and durable immune tolerance in mice by preventing T cells from attacking the myelin sheath.

    "Using a clinically tested gene therapy platform, we are able to induce very specific regulatory cells that target the self-reactive cells that are responsible for causing disease," says senior study author Brad E. Hoffman of the University of Florida. "In contrast, most current therapies for autoimmune diseases such as multiple sclerosis are based on general immune suppression, which has various side effects or complications."

    http://www.cell.com/molecular-therapy-family/molecular-therapy/fulltext/S1525-0016(17)30413-6

    https://medicalxpress.com/news/2017-09-gene-immunotherapy-multiple-sclerosis-mice.html

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  20. An axonal therapy

    Disarm Therapeutics has completed the first round of financing to develop a compound that prevents axonal degeneration in patients with multiple sclerosis (MS) and other neurodegenerative conditions.

    The treatment approach is based on an earlier discovery at Washington University in St. Louis, showing that the enzyme SARM1 is a key driver of axon degeneration, a process that causes disability and progression in several diseases of the central, ocular, and peripheral nervous systems.

    https://multiplesclerosisnewstoday.com/2017/09/21/disarm-therapeutics-to-begin-developing-multiple-sclerosis-therapy-prevents-axonal-degeneration/

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    1. "The outcomes of the project are, however, far from clear. Another recent study, published in the Journal of Neuroinflammation at about the same time as the Neuron article, questioned the feasibility of preventing this type of axonal degeneration in slowing MS-related disability, based on experiments in mice."
      "Our data indicate that in multiple sclerosis, ongoing demyelination in focal lesions is associated with axonal degeneration in the perilesional white matter, supporting a role for focal pathology in diffuse white matter damage. Also, our results suggest that interfering with Wallerian degeneration in inflammatory demyelination does not suffice to prevent acute axonal damage and finally axonal loss."
      https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-017-0831-8

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  21. No way!

    Research and Development Spending to Bring a Single Cancer Drug to Market and Revenues After Approval

    These results provide a transparent estimate of research and development spending on cancer drugs and show that the revenue since approval is substantially higher than the preapproval research and development spending.

    http://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2653012

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  22. MS aggravated by stress and stress related Epstein Barr virus reactivation.

    I wondered about the following paper gives us any insights?
    Stress-related Epstein-Barr virus reactivation. Clin Exp Med. 2010 Mar;

    'There was a significant difference between the rates of acute infection and reactivation among subjects with elevated cortisol and epinephrine levels in the second samples compared to subjects with normal levels (P < 0.001).'

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  23. I just watched a neurologist on a recent video say that DMT's prevent relapses. Maybe i'm splitting hairs but I thought they reduced relapse rate rather than prevent relapses? I think this is important to think about.

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  24. I have MS and I had seen psychological services some time ago. I was not copied into letters to my neurologist from the psychological services. I figured out several months later I should have received copes of these letters. I requested copies and was sent them but to my surprise there was a diagnosis in the letter which I was not informed about in person!

    It baffles me....

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  25. Prof G, In your post a while back on the NHS crisis you mention falls leading to unplanned hospital admissions for pwMS.
    There's a free MOOC short online course course on falls called Ageing well that might be useful for pwMS.

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  26. Mouse Doctor, you said above the spasticity trial is over. Has it been successful. If it has when I can I have it please?

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    1. There was a tweet saying the trial was fully recruited in July, but I am afraid you won't be getting the result from me. I will keep stum until the result is put in the public domain by others.

      Given that the AAN abstract deadline in mid October I would see ECTRIMS 2018 would be more likely platform for public presentation as positive or negative, I don't know if there is a late breaking deadline for the AAN, but given my disappointment with the result for this years selection at ECTRIMS 2017.

      However the fate of the trial will appear in the financial media before then...as occurs for all other news...... I think if a sale to Ipsen who have first refusal, is announced it will say something good.
      It will then be up to them what they want to do...hopefully not park it on a shelf. However, more trials will need to be done but I will have no control of what gets done.

      Delete
    2. If there is another trial, which I hope there is, then please consider to volunteer, but the nice thing is we have shown experimentally and put in the public domain that not only is their symptom control potential but the drug is also neuroprotective.

      CoI: I will gain financially if this treatment ever make it to market

      Delete
  27. Chronic Fatigue Syndrome: EBV, Women, RTX, Cyclophosphamide, antivirals

    http://www.pharmaceutical-journal.com/news-and-analysis/features/fresh-evidence-points-to-a-cause-and-possible-treatments-for-chronic-fatigue-syndrome/20201439.article


    P.S. "Fluge counters that B cells, which mature into plasma cells, can singularly produce vast quantities of antibodies, “you only need one to be pathogenic to cause problems”. It’s a waste to eliminate all the B cells, he adds, and eventually he wants to identify the specific antibody."

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