About the author



  • Hello,

    I am 28, female and living in The Netherlands.
    I was diagnosed in June 2017 (bilateral internuclear ophthalmoplegia) + migranes + nausea + sensory symptoms. MRI showed 5 non-enhancing brain lesions (one of them in brainstem). Lumbar puncture revealed the presence of oligoclonal bands.

    INO resolved but I still have some mild sensory symptoms and fatigue.
    3-month followup MRI (end of Aug) showed no changes in lesion load/volume.

    Started with 40mg Copaxone end of September.

    Question nr 1: Dr recommended MRI at 12 months after Copaxone start, but should I also maybe rebaseline at 6 months after Copaxone start (right before it reaches therapeutic levels)? Because if any lesions are found at 12 months how can I know whether they were created before or after Cop started working?

    Question 2: Would I be a good candidate for Cladribine or Alemtuzumab?

    Question 3: I also have vit D deficiency. What would be a good supplementation dose for me? Dr recommended 800IU/day, but isn’t this a bit low? Can vit D have a beneficial impact on my disease?

    Thank you beforehand for your reply.

    Best regards,

    • as I know INO is a result of a relapse which involved the Brain stem or Posterior fossa! This is a highly alarming. My sister had similar and she progressed quite fast (after 2 years from EDSS 1,5 to EDSS 3,5). Her neuro did not want to switch we looking for another who helped. She is stable with Gilenya. If I would be in your place I try everything to change a highly effective therapy. Cause you a young lady you should change to Cladribine or Alemtuzumab! (Ive answered your Q2 without reading.) Switch-switch-switch.

      Q3: vitD recommended 4-5000 IU daily! Please write an email to the Vitamin D council!

    • Thanks a lot for your reply, but isn’t that supposed to be a q&a where doctors reply?

      I am indeed very alarmed now by your answer, because I ve visited a couple of neuros, and nobody wanted to switch me.

      Is it the case that all cases that start with INO progress fast?

    • Question 1. Good point Re-baselining gives you an oppertnity to check efficacy, The question is how long does it take to get efficacy.

      Question 2. To get alemtuzumab you need to be active (MRI lesion in Europe) and for cladribine highly active. We can't give personal advice. I am not a doctor. Each persons circumstance are different and you need to talks these things through. The blog is not the place for consultations.

      In the UK there is a situtation that copaxone is not considered cost-effective but it is a relatively safe agent.

      Question 3. See the post below your question there are lots of posts. Try the search function.

      The are stuff in education I think in research day that talks about potential prognosis and what number of signs I would never say always as you invariably get exceptions

    • Thank you for replying to me and I am sorry I posted a personal question. I am new to this blog and I realised it after I posted it.

      Would there be any chance that Dr Giovannoni replies to my questions? I could give you my email if that’s not really the place for him to do so.

      I would really really appreciate that.

      Best regards

  • Hello. I would just like to ask given the push now on to develop neuroprotectors to help treat patients with MS, can you see any that may become available fairly shortly and if so do you think that the first round of neuroprotectors will only be useful in patients with relapse and remitting MS or can you see them providing protection for all MS patients? Also do you think that neuroprotectors will supercede current DMTs and the current therapeutic need to suppress or modulate the immune system or will it be more likely that they will be used as an add on to current treatments? Thank you.

    • Neuroprotectors are needed for everyone with MS there is damage to nerves from start to finish and inflammation start to finish we need to layer treatments rather than monotherapies. The problem you have now is because you have effective DMT so to do trials ethically you will need to have DMT in the trial. You may get a DMT that have neuroprotective and anti-inflammatory but mechanistically additinal neuroprotective

      Can I see if any become available shortly…I bet you have them already as symptomatic agents may well have neuroprotective activity.

    • As someone with ~2 decades of (slow) PPMS who – despite some of the repeated and forceful opinions of your team – is not about to knock 7 bells out of their immune system, I would like to see a lot more discussion of neuroprotectives on here.

      "I bet you have them already as symptomatic agents may well have neuroprotective activity."

      Which agents? I don't require/take any symptomatic drugs at all at the moment.

    • One thought of how nerves get damaged is because they are working too hard and get exhausted and they get toxic amounts of calcium Ions. Therefore drugs that stop the excitatory ions from developing will probably be neuroprotective. There are a large number of possible treatments that do this.

      The problem is there is no evidence in humas so I won't name the drug names,

  • Hello!
    I am looking for information on estrogen therapy for MS. Why is this not a hot subject for research?
    I have MS and the only real symptom free periods in my 10 years with MS were my 2 pregnancyes and 6 months on estrogen patch. However I developed ovaryan cysts so my gyno stopped estrogen. 2 months after my last estrogen patch I am in a biggest relapse ever.

    What are your thoughts on estrogen and MS?
    Thank you,

    • Why is there not hot,…there is little pharmaceutical interest and also MS affects men too.

      The effects of hormones in MS is well known and pregnancy used to be the most effective DMT,

  • Hi there,

    I've posted this before, but my comments never seemed to publish, so my apologies for the repetition! What are your thoughts on using mass spectroscopy for use in dx of CIS in the absence of any lesions on MRI? More specifically the NAA, choline, and creatine ratios can suggest a demyelinating event that isn't picked up as lesions in the early stages of MS.


    All of these seem to support using mass spec as a means of measuring active MS, but what about those patients that are experiencing MS-like symptoms in the absence of lesions? Should they be labeled as CIS? Should DMTs be started?

    Thanks so much for your input!

    • MRS is not common. NAA also has problem as it was used as a measure of nerve content but it NAA loss can recover so what is it really measuring and for dx you need lesions in "time and space"..does mass spec give you the in space?

      I'm not a neuro

    • Thanks ever so much for your reply.

      MRSI is becoming more common (here in the U.S., that is) and reports are usually given as a Z-score from the callosal and supra callosal areas of the brain, so if levels are different, hypothetically this could give you the "in space" needed.

      CIS is a first MS-like event, so my question is: if this is a flag for early disease activity, shouldn't more action be taken to preserve what has not yet been lost?

      Thanks again for your answer.

    • I personally think treat early this is why it was suggested natalizumab might be a good first option to stop further episodes whilst working on diagnosis.

    • Thanks again for your input. This blog is one of the best resources right now for people living with MS and their caregivers, be they in the medical field or not. While you may not hear is nearly enough, thanks so very much for all that you do.

  • Sorry I commented in the wrong publications.

    In my last consultation now in December 2017 it really comes down to the fact that MS affects a lot more women than men. There were only two men for about 12 women who would be seen on the day of my routine appointment.
    So I'm interested in the gender difference in MS, and how hormones can influence it.

    Testosterone sends mast cells to secrete IL-33 in males. It appears that IL-33 (or "guarded molecule" as it was called) triggers a series of chemical reactions that block the development of Th17 immune cells.


    And it will be one of the posters of ACTRIMS 2018, two teenagers developed MS shortly after taking the HPV vaccine.

    They didn't conclude whether it was a "coincidence" that they developed MS, or whether the vaccine was somehow recognized as an antigen by a deregulated immune system, or whether the vaccine actually triggered the disease.

    Here in Brazil we have had some reported cases of girls who took the HPV vaccine and who, as it turned out, developed Guillain Barre Syndrome.


  • I've noticed of late patients questions
    Via comments are not being answered. Which is okay as fulltime researchers you will not have time. So why allow patients to ask questions and then not answer them? I personally think you spend the time finding a cure. But We both know that's not going to happen. pharma money will buy it and lock it in a vault. There will be no cure for ms until another cash cow appears.

    • If ProfG throws in a curve ball, he will need to answer the comments. His new post has sparked considerable debate internally and externally

      If MS is autoimmune and we know the antigen I know what we would do, we have done it in animals hundreds of times but as we have shown there is no quick answer because the way the scientific process has been allowed to develop.

      The best way to a cure is treat early abd effectively

    • We are not allowed for medicolegal reason to answer patient-specific questions. What we can do it generalise the questions.

  • Why did ocrel show better results than lemtrada or tysabri in that 40.5/53 paper making a storm on social media?

  • What are the possibilities for slowing the progress of the disease us with the diagnosis of G37, mild pleocytosis and OBS negative CSF, ANA nucleoplasmic homogeneous positive, without any other symptoms or findings suggestive of systemic connective tissue disease, and with over 10 lesions on the brain and spinal cord. How many people are in such a situation? Whether the prognosis is better or worse than the classic ms?

  • Mri usefullness

    "We also assessed the predictive value of MRI metrics
    commonly measured in MS clinical trials over 2-year
    intervals, and found no association between new T2
    lesions or gadolinium-DPTA–enhanced lesions and worse
    long-term outcomes."

    Edss increase over 2 yeras its not predictive

    "Similarly, an increase in the EDSS score over 2
    years was not associated with worse long-term prognosis.
    Thus, short-term increases in EDSS do not necessarily
    predict future accumulation of disability in RMS patients
    over the longer term, a conclusion also reached in a
    pooled analysis of patients randomized to placebo arms in 31 clinical trials.48"

    Neda (For what ?)

    "Because neither clinical nor radiographic
    features over 2 years had predictive value, it is
    not surprising that the combined measure of these variables,
    NEDA, was also not associated with long-term disability
    risk. Although this observation must be
    interpreted with caution because of the relatively small
    number of NEDA patients in our cohort, another recently
    published observational study also found that the proportion
    of patients meeting a NEDA definition declined
    substantially over time.49 These observations challenge
    the concept that NEDA represents remission. Although
    NEDA may be a useful measure for assessing relative
    therapeutic efficacy, many patients who meet NEDA criteria
    over 2 years go on to develop clinically significant
    disability. Worsening in patients who meet the 2-year
    NEDA endpoint could result from active spinal cord disease
    not captured with brain MRI, progressive axonal or
    neuronal degeneration, or an escape from a true but transient
    remission state. A recent study that incorporated
    thresholds for acceptable brain volume loss for NEDA
    found that one-third of NEDA patients treated with fingolimod
    still experienced significant brain volume loss
    during the NEDA interval, indicating that ongoing tissue
    injury occurs in NEDA patients.50"

    Long-Term Evolution of Multiple Sclerosis
    Disability in the Treatment Era

    ANN NEUROL 2016;80:499–510


  • Autoimmune disorders such as rheumatism or type 1 diabetes are on the increase world-wide. Regulatory immune cells protect healthy individuals from the disorders and combat disease progression in affected individuals. So far, little is known about the group of regulatory B cells which play a role in this context. Researchers of the Paul-Ehrlich-Institut (PEI) and the University Hospital of Würzburg found a marker, the tumour necrosis factor receptor 2 (TNFR2), which makes it possible to identify and enrich these cells. Frontiers in Immunology published these research results online on 19th January 2018.

    Expression of Tumor Necrosis Factor Receptor 2 Characterizes TLR9-Driven Formation of Interleukin-10-Producing B Cells



    • Thanks I will have a look but my concern is this automatic jump that IL-10 producing cells are regulatory.

      They may be but IL-10 is a B cell growth and differentiation factor so IL-10 producing B cells may simply be present to promote B cell growth. Likewise tumour necrosis factor is a B cell survival factor so not surprising that they express TNF receptor. Many of the B cell markers are part of the TNF superfamily

  • News from Biotin

    A key finding was that MD1003 led to significant improvements in patients’ EDSS and TW25 scores at nine months, compared with the placebo-treated patients. The treatment’s benefits held at 18 and 30 months, researchers said.

    After the placebo group switched to MD1003 at nine months, researchers saw no differences in new EDSS results between the treated and control groups at months 24 and 36.

    But the group that received MD1003 for the first nine months continued to have better cumulative scores than those who initially received a placebo, then switched to MD1003. This suggested “that earlier treatment leads to a lower disability” at month 36, researchers wrote.

    Another finding was that at one year the patients who were initially treated with MD1003 performed better in the time to walk 25 feet test than the controls. This held during the follow-up period. In contrast, the performance of the group initially treated with a placebo worsened in the final year.

    In addition, the Clinician and Subject Global Impression scale results were significantly better in the MD1003-treated group during the first year, but there was no difference after that.



  • Ozanimod

    The higher dose of ozanimod reduced the number of T2 lesions by 48 percent and the lower dose by 25 percent. The larger dose reduced T1 lesions by 63 percent and the smaller dose by 34 percent.

    Ozanimod also slowed brain volume loss. In the thalamus, the higher dose led to it slowing the loss by 39 percent and the lower dose by 34 percent, compared with Avonex. In the cortex, the larger dose led to brain volume loss slowing by 84 percent and the smaller dose by 61 percent.


  • Quick question about barts EDSS SCALE. Regardless of other symptoms. It says for walking. 8km on 3 hrs or 10km in 4 hrs 8s edss of 0. Is that non STOP? For instance someone who walks 5 km in 1 hr 15 mins. The walks 3 km in 1hr and 45 mins with rest is that the same? Is it total distance or the total distance non STOP?

  • Cladribine in ACTRIMS:

    Effects of cladribine tablets on CD4+ T-cell subsets in the ORACLE-MS study: Results from an analysis of lymphocyte surface markers

    Conclusion: The first administration of cladribine tablets has a comparable magnitude of effect on CD4+ T-cell subpopulations, with no dramatic shifts in proportions. Further investigation is ongoing to explore the implications for the mechanism of action of cladribine tablets and the effects of treatment initiation at Year 2.

    Long-term lymphocyte counts in patients with RRMS treated with cladribine tablets 3.5 mg/kg: Total lymphocytes, B-, and T-cell subsets

    Lymphocyte recovery begins soon after CT treatment, with ALC, CD19+ B cells, and CD4+ T cells recovering and reaching threshold values by 7.5 months, 12 months, and 18 months, respectively, after the last dose in Y2. CD8+ cells never dropped below the threshold value.


    Alemtuzumab and Cladribine: A Comparison of Pharmacodynamics and Mechanism of Action

    Results: Alemtuzumab, a humanized monoclonal antibody, selectively depletes CD52-expressing T and B cells by antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Following depletion, a relative increase in regulatory T cells (Treg) and decrease in proinflammatory cytokines occurs, potentially leading to rebalancing of the immune system. B cells return to baseline levels within 6 months; T-cell levels generally reach lower limit of normal by 12 months. The distinct pattern and time course of lymphocyte repopulation are consistent across treatment courses. Alemtuzumab restores Treg function by promoting long-term increase in Treg suppressive activity against myelin basic protein-specific Th1 and Th17 cells. Cladribine, a synthetic purine analogue, enters cells and is incorporated into DNA, leading to cellular apoptosis and/or autophagy. Cladribine is selective for lymphocytes due to their relatively high levels of drug-activating deoxycytidine kinase and low levels of drug-inactivating 5′-nucleotidase. After cladribine treatment, lymphocytes reach a nadir by 9 weeks (wk). In a clinical trial, slight lymphocyte recovery occurred before re-dosing at Wk 48. Reduced median lymphocyte counts persisted to Wk 96. Cladribine caused greater suppression of T than B cells in both the short and long terms, with modest decreases in neutrophils at Wk 96. Cladribine PD may include regulation of cell cycle, signalling, and proliferation genes; cladribine may also modulate pro-inflammatory cytokine profiles.

    Durable effects of alemtuzumab, an approved high-efficacy MS therapy, may be due to its selective depletion and distinct pattern of repopulation of circulating T and B cells thought to play a role in MS pathogenesis. Cladribine (approved in the European Union for the treatment of highly active relapsing MS) induces T-and B-cell apoptosis, in part by suppressing DNA synthesis and repair. These distinctions in MoA and PD may underlie differences in short- and long-term efficacy, safety, and the potential need for retreatment.


    Neutrophil and monocyte cell numbers remained within normal limits in patients with RRMS treated with cladribine tablets 3.5 mg/kg

    Conclusion: These data, together with the previously reported data on ALCs, support the concept that CT selectivity reduces adaptive immune cell counts, with a relatively minor impact on the innate immune system.


    Safety and Efficacy of Intravenous Cladribine in Multiple Sclerosis Patients


    • We published all of this month's ago so it is not news and hardly worth a poster. It's open access in neurology n2.

    • However it doesn't stop someone from traveling on the coat tails of pharma. The people selecting the posters need to open their eyes to what is old news. However, are they going to turn down a company sponsored poster. I guess not 🙁

  • Alemtuzumab in ACTRIMS:

    Alemtuzumab: Paradoxical effects on autoimmunity in individuals MS

    Secondary autoimmunity after alemtuzumab is a significant clinical problem, that requires a careful risk monitoring plan. It appears to arise from homeostatic proliferation of the peripheral T lymphocytes remaining after alemtuzumab, and failure of the thymus to restore the T cell repertoire. No predictive biomarkers exist, but there are hints that serum IL-21 may provide this in the future. A treatment which promoted thymic function after alemtuzumab may reduce autoimmunity, but none has been tried to date.


    (Different approach to Barts)

    Durable Improvements in Relapse and Disability Outcomes over 7 Years with Alemtuzumab in CARE-MS II Patients: Results from the TOPAZ Study

    Conclusion: Clinical efficacy of alemtuzumab was durable for 7 y in pts who had inadequate response to prior therapy, despite 47% receiving no further treatment since the initial 2 alemtuzumab courses. The majority of pts maintained low ARR, were relapse-free, showed stabilized or improved disability, and achieved NEDA in each year.


    (More than half needed 3rd dose)

    Efficacy of Alemtuzumab Retreatment in Patients Who Experienced Disease Activity after the Initial Two Courses: Results from the CARE-MS II Extension

    These data support that in the CARE MS II extension, patients who experienced MRI activity or relapse after Course 2 benefitted from retreatment with a third alemtuzumab course, which can reduce relapses and improve disability.


    (Will NICE read that?)

    • Thanks we have suggested that driving new cells out of the thymus may not be the way to stop secondary autoimmunity. There results are not in the slides, but the abstract indicates the approach fails because the treatemnet does not cause cells to come out of the thymus in contrast to that found in monkies. However ma and miceybe this could have been expected as palifermin didnt do cause thymic output in an earlier study (Jacobson et al 2014).

      The CARE Extension data is already reported

  • Miscellaneous

    Gene Therapy: An In Vivo Approach to Induce Immune Tolerance, Inhibit Neuro-Inflammation and Disease, Regardless of Genetic Background

    Results: Following EAE induction, Null mice began developing clinical signs of severe ascending paralysis, while AAV.MOG treated mice remained virtually symptom free (mean peak scores for Null vs AAV.MOG as mean±SEM for each epitope combination) [C57BL/6: 3.3±0.8 vs 0±0; 3.7±0.2 vs 0.25±0.3, and DBA/1: 3.5±0.4 vs 0±0]. Null mice also had substantial inflammation compared to AAV.MOG mice.

    Conclusion: In contrast to approaches using ex vivo engineering or expansion of Ag-specific Tregs, we have demonstrated that AAV8.MOG gene therapy can dynamically induce immune tolerance in vivo to multiple immunogenic epitopes of MOG which inhibits neuroinflammation and disease, regardless of genetic background,. Eliminating the need to identify HLA/MHC specific epitopes, makes this approach universally applicable as an effective therapy.


    Glunomab®: A Novel “Barrier-Protecting” Monoclonal Antibody Efficient in Mouse Models of EAE.


    We observed that this antibody binds NMDAR located at the luminal surface of neurovascular endothelium at the vicinity of tight junctions of the blood-spinal cord barrier. When injected during the effector phase of Experimental Autoimmune Encephalomyelitis (EAE), it blocked the progression of neurological symptoms.


    This therapeutic effect was associated to a preservation of the blood-spinal cord barrier, leading to reduced leukocyte infiltration. Overall, this study unveils a critical function of endothelial NMDAR in MS, and highlights the therapeutic potential of strategies targeting the protease-regulated site of NMDAR.


    • AAV.MOG is probably not going to go anywhere in MS. Responses to MOG are more associated with a type of NMO. There have been hundreds of MOG protein studies like this.

      Blocking NMDAR with an antibody will be bad news, only weak blockers eg. memantine are tolerated as NMDA receptors are useful.

  • Miscellaneous from ACTRIMS II

    Low Dose Naltrexone in Multiple Sclerosis: Web-Presence Versus Scientific Evidence

    Results: We screened a total of 24 articles and included 18 publications (7 clinical investigations, 6 preclinical studies, 1 medical hypothesis, 4 commentaries). We excluded 6 studies irrelevant to MS. We found 3 clinical trials for LDN in MS patients which suffered limitations, and none provided conclusive evidence on the subject. However, all studies agreed on the safety of LDN. Google searches for the term “naltrexone and MS” yielded about 413,000 results and for “low dose naltrexone and multiple sclerosis” yielded about 184,000 results. Numerous patient-oriented websites discussed LDN and MS with phrases used such as “Overcoming Multiple Sclerosis” or “A Wonder Drug that Eases Multiple Sclerosis Side Effects,” among other claims. A limited number of websites, such as the National Multiple Sclerosis Society, provided evidence-based information for patients and caregivers on the subject and acknowledged the limitations of the scientific evidence

    Conclusion: It remains challenging for health care providers to answer various patient queries regarding potential effects of LDN in MS due to the inadequacy of clinical evidence. We identified a gap between readily available information off the internet for MS patients and actual scientific evidence. Preclinical investigations showed promising effects on inflammation and disease modification. Further studies are needed to determine the effect of LDN as an add-on therapy on quality of life measures such as pain, energy, social, cognitive and sexual functions in patients living with MS


    Vitamin D Supplementation May Have Therapeutic Effects in Neuromyelitis Optica Spectrum Disorder

    Conclusion: Physiological variation in vitamin D may exert a major impact on autoimmune and inflammatory disease. We observed that vitamin D supplementation can decrease IgG-NMO, EDSS and fatigue scale in participants with NMOSD and vitamin D supplementation may have therapeutic effects in NMOSD.


    Brain Atrophy after High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Multiple Sclerosis (HALT-MS)

    Brain volume loss may accelerate for months after HDIT/HCT due to the effects of chemotherapy-related toxicity and progression of WM lesion-related degeneration. However, over the long-term, adequate immunosuppression and HCT can reduce rates of brain volume loss to the range observed in normal aging.


  • MS Hypothesis:

    Hypothesis: Multiple Sclerosis Is Caused By a Sequential Double Hit of Two Common Infections.

    Results: We propose a three-tiered hypothesis: 1) a model to explain clinical and epidemiological phenomena which argues that multiple sclerosis is a rare late complication of two sequential infections (with the temporal sequence of infections being important); 2) a proposal that the first event is infection with the helminth, Enterobius Vermicularis, and the second event is Epstein Barr Virus infection; and 3) a proposal for a testable biological mechanism to explain the model.

    Conclusion: We believe that this model satisfies many of the as-yet unexplained features of multiple sclerosis epidemiology, is consistent with the clinical and neuropathological features of the disease and is potentially falsifiable by experiment. This model may have elements which are relevant to other autoimmune diseases.


    Is MS a Transmissible Protein Misfolding Disorder?

    Results: MS-injected mouse brains exhibited significant degeneration of myelin with microglial activation in the corpus callosum, leukocortical junction and peri-ventricular region, assessed by QD9 and Iba-1 immunohistochemistry. Formic acid-resistant prion protein aggregates were detected in both white and gray matter regions. Protease resistance, often seen in more conventional prionopathies, was not detected in either human MS brain nor MS-inoculated mice.

    Conclusion: Our results are consistent with the hypothesis that MS may be a primary degenerative disorder caused by accumulation and propagation of atypical pathogenic prion protein, that can transmit pathology to humanized murine hosts. We speculate that these toxic pathological conformers are may circulate in the CSF and spread to various brain regions. The resulting degeneration of myelin and release of antigenic debris could secondarily trigger an autoimmune inflammatory response in genetically and environmentally predisposed hosts. Together, such a convolution of a primary prion-dependent degeneration, with secondary inflammation could explain the broad spectrum of human MS phenotypes. Our observations may shed light on the fundamental cause of MS.


    Multiple Sclerosis Patients Have a Increased Cellular Response to Autoantigens Which Cross-React with Proteins from Epstein-Barr Virus.

    Results: We tested the cellular response in 15 MS patients and 5 controls. Six MS had a proliferative response to septin-9, two to HNRNPL, and one to DLST. The maximum stimulation index for septin-9 was 4.8. No patient responded to more than one antigen. None of the controls had a proliferative response to any of the three antigens.

    Conclusion: A subset of MS patients has a T cell proliferative response to the autoantigen septin-9. Further investigation with larger numbers of patients and controls is needed, along with determination of the cytokine profile and phenotype (CD4 vs. CD8) of the responding cells. This work suggests a unique mechanism for autoimmunity, whereby B cells producing an anti-EBV immunoglobulin which cross-reacts with a self antigen stimulate an autoreactive T cell response. If further work supports the pathogenic potential of the septin-9 reactive T cells, then induction of tolerance to this antigen would be an attractive approach to an effective, antigen-specific treatment with minimal toxicity.


    • New Idea MS is caused by pin worms and EBV. Is the new idea?.
      The pinworm causes you to get an itchy bum as the worm exits your body, scratch and not clean your hands and you re-infect.

      Do you rembeber having worms…No. idea down i flames, however the poster was about the cause of MS in the Faroes during WWII.

      Is it a prion disease.

  • Axonopathy & Remyelination:

    A Novel In Vivo Screen for Oligodendrocyte Differentiation and Myelination

    Results: GC1, a thyroid hormone receptor agonist, significantly increased mpz promoter activity. Transgenic zebrafish are well suited to establish the details of the drug’s pro-myelinating effects, and our studies demonstrate that GC1 increases myelin internode length and number and myelin RNA levels.

    Conclusion: This novel in vivo zebrafish screen is currently in use, screening pathway-specific libraries for new drugs to enhance myelination.


    A Novel Subset of Neutrophils Induces Axon Regeneration Following Transection

    Conclusion: A novel subset of Ly6GlowCD14+ neutrophils is capable of driving regeneration of transected CNS axons. These cells secrete a pro-regenerative soluble factor, and recruit arg+ CD206+ monocytes to the site of injury. Our findings may lead to the development of novel immunomodulatory drugs, or the repurposing of immunomodulatory drugs already in clinical use, to promote the differentiation and expansion of neuroregenerative neutrophils in patients with axonopathy, including MS.


  • This recent study – https://plan.core-apps.com/actrims2018/abstract/09be07f9cacd4c5743fd28fd3758a3f8

    is slightly different than research released at ECTRIMS this year:


    You have one poster session, this article citing, ACTRIMS presented research, saying Biotin slows disability and ECTRIMS (link I include above) urging caution – made things worse, at least as measured by MRI and relapses.

    ECTRIMS – smaller sample and measuring relapses and MRI activity
    ACTRIMS – no info on whether they used MRI or just monitored changes in 25TW test. Makes me wonder about disclosures/sponsors and whether Biotin good or bad. Should I be taking? I have Progressive MS. Longest time docs thought I have RRMS – really have PPMS or SPMS – never had a relapse.

  • Oh, and as fu to last comment – what weight ("dose") of this would then be recommended, if suggestion is to supplement? Any side effects to high dose b7?

  • The results of the clemastine fumerate study were "modest" in regenerating myelin. I had difficulty finding the original study so not sure, but clinically significant, no? I would call the effects of the first line DMDs modest-imagine if I only showed up at work 35% of the time! I took the max dose of CF and had no side effects. Bonus: no more allergies. Wouldn't it be best practice to put all RRMSers on CF? Thanks for your time guys.

  • My husband is in stage two with his MS is treatment with stem cell a positive or is it negative for him. We found a hospital in Mexico that will do the stem cell treatments but I really need to find a study in the United States that he can get into. Please help I'm at a loss now and we need him around.I'm scared and don't know what else to do.

  • Cervical spinal cord atrophy
    An early marker of progressive MS onset


    Conclusion Cervical spinal cord atrophy is evident at the onset of progressive MS and seems partially independent of the number of cervical spinal cord lesions.

    Classification of evidence This study provides Class III evidence that MRI cervical spinal cord atrophy distinguishes patients at the onset of progressive MS from those with RIS and RRMS.

    • The following is a list of deaths on other DMTs:

      Gilenya = 503
      Tysabri = 3009
      Lemtrada = 75
      Tecfidera = 938
      Aubagio = 269
      Copaxone = 730
      Rebif = 1686
      Betaseron = 1171
      Avonex = 6343
      Plegridy = 86
      Zinbryta = 25

      What does it mean? Does it mean all DMTs are linked to deaths?

    • A death is an adverse effect and gets reported. However it could be a car accident someone choking on a fish bone and have nothing to do with a drug side effect.Also you need to know how often the drug is being used to get an idea if there is something unusual.

      However that you can find such information shows that the company's are taking the monitoring of their drugs seriously

      I would be most interested in the deaths related to infections.

    • 45 deaths in 6 months seems a lot. Zimbryta was banned from EMA for 2 deaths. It seems that at least the drug needs to come with certain guidelines, like Tysabri. Doctors seem to be concerned not only for the respiratory infections but also for heart related issues. It could be something that the right dosing could fix. But for now it looks concerning.

      "However that you can find such information shows that the company's are taking the monitoring of their drugs seriously"

      Hmmm (?)

  • It's been reported as well as 48% in brain atrophy, Ibudalist reduced disease progression by 25% compared to placebo. When thia was first reported in Ectrims 2017. Barts thought it was too early to claim success as there was no data in clinical outcome. As much as I admire barts team for their research in MS. But isn't it time to truly eat humble pie and do a post on ibudalist and it's potential mechanism for working? Or become part phase 3 trials?

    • Time to eat humble pie, not really, we will do a post when the data is published, we have seen it presented but would like to see the paper.

      As to its potential mechanism for working

      how many do you want?




      I was predicting disease activity in some people


      Happy that if this didnt happen, but we then have to think the PDE4 activity is not important or is telling us something.

      Here is how the company says it works
      It is small molecule glial attenuator that suppresses pro-inflammatory cytokines IL-1ß, TNF-a, and IL-6, and may upregulate the anti-inflammatory cytokine IL-10. It has additionally been shown to be a toll-like receptor 4 (TLR4) functional antagonist that may contribute to its attenuation of neuroinflammation.

      While considered a New Molecular Entity, or NME, in the United States and Europe, it involves redirection of an approved drug, ibudilast, which was first approved in Japan more than 20 years ago. Ibudilast has been prescribed to over 3.2 million patients and has a good post-marketing safety profile.

      As for clinical trial…if the US company had supplied the drug for the MS-SMART (multi centre trial throughout the UK including Barts) as requestedd the second trial would now have been finished. They did prozac because of this.

      As for phase III, I dont know about this.

    • Thanks MD. At least the ground is starting to move for Progressive and Secondary. Do you have any positive views of statins phase 3 trial in 2nd progressive?

    • Yes I have some positive views

      This reminds me to write paper on potential mechanism of action as the answer I got from one of people behind the study was useless.

      The genetics and an increasing number of studies point towards the cholesterol pathway as being important in neurodegeneration in MS and Alheimers. There is positive data from the phase II and hopefully this will repeat.

      However, with a pharma hat on, I would say the phase 3 has a flaw in that there is no dose-response. They are sticking with the high dose that will cause side effects for some without proving the lower, standard dose is ineffective. However to do a lower dose it would make the cost too high to add an extra 500 people in the study.

      So the regulators should say go away and prove that a lower safer dose does not work. Will they do this.

      I guess the view is do the trial and everyone will change…people power but it means it is one rule for pharma and a different rule for the rest.

      So the question I have is this, what happens when the trial is positive. What happens then?

      We all start using statins, but will it be better than siponimod or ibudilast which has done one trial, if it siponimod gets a licence you would need two statin trials if you have to do it like pharma.

      I guess it is better to do something rather than nothing, but it is clear that MS is inflmaatory from beginning to end and is neurodegenerative from beginning to the end so why not try deal with both problems?

  • Stumbled upon Biocad’s BCD-132 anti-cd20 mee-too Patient Informed Consent, and it states that there is possibility that BCD-132 could be used as induction therapy and one of the study purposes is to determine if it really works like that. So I wonder is there any data around to show that anti-cd20 are induction therapies? Everything I heard is that they are used once 6-9 months.

  • Hi I know I'm asking a personal question. I've been a fitness fanatic all my life and is how I knewni had ms before my ms. In ask this question in help others as well as myself. I'm 5 months post Alemtuzumab. I have bloods every month. And I'm a scientist but not medically tainded. Today both my face and palms are red. I'm think skineed and not fair. I have gone through all the scenarios and it doesn't add up. To help me and others. After alemtuzumab. Any ideas?

  • Hello. Apologies if this is obvious or has been answered before. Are oligoclonal bands the cause of the damage, or as the result of the damage?

    • The presence of oligoclonal bands of oligoclonal bands is the source of much debate. They don't seem to be either a main cause of damage or as a result of damage as they don't seem to be a target of antigens in the brain but I've been thinking about this and a I think they might be significant in the longer term as a source of microglial cell activation.

  • This was posted on ProfGs twitter and seems very interesting. Can you comment?

    Differential diagnosis for neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) is always doubtful. To differentiate these diseases, we studied the immune status in the blood of patients with MS (n = 45) or NMOSD (n = 23) at remission phase. Remitting NMOSD patients had increased levels of CXCL13 and memory B cells, while remitting MS patients had elevated levels of galectin-9 and Th1 cells. A diagnostic model with these four variables is built to distinguish remitting NMOSD from MS with a sensitivity of 91.30%. Our diagnostic model may help to improve the differentiation of remitting NMOSD from MS.


  • Do antidepressants make MS fatigue feel worse? I ask this as antidepressants can cause lethargy and overwhelming tiredness.

  • Study from the Department of Clinical Neurosciences at the University of Cambridge
    Scientists have shown in mice that skin cells re-programmed into brain stem cells, transplanted into the central nervous system, help reduce inflammation and may be able to help repair damage caused by multiple sclerosis (MS).

    Using mice that had been manipulated to develop MS, the researchers discovered that chronic MS leads to significantly increased levels of succinate, a small metabolite that sends signals to macrophages and microglia, tricking them into causing inflammation, but only in cerebrospinal fluid, not in the peripheral blood.

    Transplanting NSCs and iNSCs directly into the cerebrospinal fluid reduces the amount of succinate, reprogramming the macrophages and microglia – in essence, turning 'bad' immune cells 'good'. This leads to a decrease in inflammation and subsequent secondary damage to the brain and spinal cord.

    "Our mouse study suggests that using a patient's reprogrammed cells could provide a route to personalised treatment of chronic inflammatory diseases, including progressive forms of MS," says Dr Stefano Pluchino, lead author of the study from the Department of Clinical Neurosciences at the University of Cambridge.


    • Thanks, I have seen this "Study in mice suggests personalised stem cell treatment may offer relief for progressive MS"

      by Dr Luca Peruzzotti-Jametti
      "It isn’t every day that you find yourself invited to play croquet with a Nobel laureate, but then Cambridge isn’t every university"

      The study says that you can make neural stem cells from inducuble pleuripotent cells made from the skin but it has been done before

      Zhang C, Cao J, Li X, Xu H, Wang W, Wang L, Zhao X, Li W, Jiao J, Hu B, Zhou Q, Zhao T. Treatment of multiple sclerosis by transplantation of neural stem cells derived from induced pluripotent stem cells.Sci China Life Sci. 2016; 59:950-7.

      Interestingly of the stem cells transplanted "a minority of cells expressing neuronal, astroglial or oligodendroglial lineage markers", so the original idea of stem cells making new nerves and oligo dendrocytes does not occur.

    • PS Does I say it wont happen in progressive MS…No

      But is a big leap from the first episode of EAE to progressive MS. The model has no real validity for modeling progressive MS… make of that what you will.

  • In Norway, rituximab has for some time been used off label for RRMS – I have had my first infusion. This anti-CD20 monoclonal antibody is chimeric, having mouse variable and humanized constant regions. I have read in the blog that 40% may make neutralizing antibodies (probably towards the mouse component), but that the titer of these may become reduced after multiple treatment cycles. Nevertheless, I worry that there is a significant risk, on an individual level, that the drug may have very low efficacy. Do you guys agree?

    Luckily, ocrelizumab is now approved in Norway. A report sited on the blog says that, for this drug, neutralizing antibodies are found in 1% only. Is this number still up to date?

    Are there any studies that suggest that it may be unsafe to switch from ritruximab to ocrelizumab?

    What about anti-CD20 and brain atrophy??

    • No, in other studies the neutralizing frequency is much lower than the 40%. There are thousands of people in sweden who are getting benefit from rituximab and the question is, do you need treatment every 6 months. I suspect not. However the antibody frequency with orcelizumab will be low based on

      ProfG may know about switching data but ocrelizuma is not yet available in England but I see now reason why it would be a problem.

    • "unsafe to switch from ritruximab to ocrelizumab?"

      Actually some think Rituximab is safer and aren't switching.


      Ocrevus’s high dosage alarms Langer-Gould
      First, the 600 mg dosage level Ocrevus was approved at was not tested adequately, Langer-Gould said. In her opinion, “it’s way overdosed and may actually be less safe than the way we use rituximab.”

      Because of this safety concern, her clinic is not planning to switch their roughly 800 MS patients off Rituxan to Ocrevus.

    • You are lucky that you are offered RTX, in America they make it more and more difficult to be on this drug (Roche pressures on that). It is higly effective (the 40% that you mention must be from Lemtrada) and it has a 20 year safety profile. Why test a new (a little controversial) drug on you?

      New paper

    • Also,

      "Nonetheless, ocrelizumab infusions in MS patients appear to be related to elevated risk of upper and lower respiratory infections, upper respiratory irritation during the infusions (typically the first infusion), peripheral herpes related infections, and some concern over malignancies, particularly breast cancers [25]. In terms of rituximab, such adverse events were not seen in our study or in prior studies. These differences in the profile of adverse events may highlight fundamental differences in the pharmacokinetic and pharmacodynamic properties of the two molecules, which remain to be explored. It is already known that the two molecules have differences in the mechanism whereby they achieve B-cell depletion. There may be important difference in tissue penetration, repletion rate, and secondary effects on T-cells"


    • As for brain atrophy, Roche hasn't released the data of O. yet, but profG believes that it will be the similar to the other DMTs, aka it will lessen atrophy but not enough.

  • Compensation of the Chief Executive Officer, Olivier Brandicourt

    (ceo of Sanofi,Genzyme) Abaugagio,Alemtuzumab

    $ 9,660,113 millions(2016)= 26 466 $ per day

    $ 16,760,008millions(2015)= 45 917 $ per day




    Results: 110 patients were randomized, 55 to each arm. Three HSCT patients were withdrawn: two for failing enrollment criteria, one for recurrent infections occurring before transplant. Five control patients were withdrawn after soliciting transplants at other centers. All patients are at least one-year post enrollment. No deaths occurred and no CTC grade 4 non-hematopoietic toxicities occurred in the transplant arm. DMTs (number of patients) used in the control arm were: natalizumab (22), dimethyl fumarate (18), fingolimod (13) interferons (10), glatiramer acetate (8), mitoxantrone (5). During the first year after enrollment, one relapse occurred on the HSCT arm versus 39 on the DMT arm (P< 0.001). Mean EDSS improved from 3.5 to 2.4 after HSCT while it worsened from 3.3 to 3.9 on DMTs (P< 0.001). With a mean follow up of 3 years (range 1 to 5 years), treatment failure was 60% (30 of 50) for the control arm and 6% (3 of 52) for HSCT (P < 0.001). For the 30 patients who failed the control arm and crossed over to HSCT, by one year after HSCT, the mean EDSS improved from 5.2 to 2.6 (P< 0.001).

    Conclusions: HSCT was statistically superior to continued DMTs in patients with RRMS with > 2 relapses a year


    • Very good. Non ablative HSCT works. Is this surprising as an immune rebooter.

      Randomising alemtuzumab/ocrelizumab vs a low efficacy DMT shows significant efficacy so am surprised that someone who wants HSCT would select GA IFN, DMF.

  • Thousands of axons grew from the transplants and connected to damaged primate tissue, the first such demonstration in primates.

    Restorative effects of human neural stem cell grafts on the primate spinal cord


    We grafted human spinal cord–derived neural progenitor cells (NPCs) into sites of cervical spinal cord injury in rhesus monkeys (Macaca mulatta). Under three-drug immunosuppression, grafts survived at least 9 months postinjury and expressed both neuronal and glial markers. Monkey axons regenerated into grafts and formed synapses. Hundreds of thousands of human axons extended out from grafts through monkey white matter and synapsed in distal gray matter. Grafts gradually matured over 9 months and improved forelimb function beginning several months after grafting. These findings in a 'preclinical trial' support translation of NPC graft therapy to humans with the objective of reconstituting both a neuronal and glial milieu in the site of spinal cord injury.

  • Oxygen sensor proteins can regulate immune B-cell activity, preventing inflammation in autoimmune disorders such as multiple sclerosis, a study reports.


    Animals lacking HIF-1α had significatly lower levels of a B-cell subpopulation that could produce the anti-inflammatory signaling protein interleukin-10, or IL-10.

    “HIF basically acts like a psychotherapist for a certain type of immune cells — the B-lymphocytes,”

    “Taken together, this study demonstrates the key function of the hypoxia-associated transcription factor HIF-1α in driving IL-10 expression in B-cells, and in controlling their protective activity in autoimmune disease,”

    The team suggested that activating HIF-1α “through pharmacologic agents may indeed provide a tool to augment the immune regulatory potential of IL-10-producing B-cells with the potential to prevent and/or treat systemic autoimmune inflammatory diseases.”

    • Hmm, I wonder if they've thought this through, Il-10 enhances B cell survival, proliferation, and antibody production. Given what we now have revealed about the central importance of B cells in MS, this might be a very bad idea.

    • CD1d(hi)CD5(+) B cells, as mentioned in the study above, are interesting. If I understand things correctly, they are CD20 negative and would thus not be depleted when I am being treated with rituximab?? Do they dampen inflammation??

      Abstract from https://www.ncbi.nlm.nih.gov/pubmed/18482568

      B cells mediate multiple functions that influence immune and inflammatory responses. In this study, T cell-mediated inflammation was exaggerated in CD19-deficient (Cd19(-/-)) mice and wild-type mice depleted of CD20(+) B cells, whereas inflammation was substantially reduced in mice with hyperactive B cells as a result of CD19 overexpression (hCD19Tg). These inflammatory responses were negatively regulated by a unique CD1d(hi)CD5(+) B cell subset that was absent in Cd19(-/-) mice, represented only 1%-2% of spleen B220(+) cells in wild-type mice, but was expanded to approximately 10% of spleen B220(+) cells in hCD19Tg mice. Adoptive transfer of these CD1d(hi)CD5(+) B cells normalized inflammation in wild-type mice depleted of CD20(+) B cells and in Cd19(-/-) mice. Remarkably, IL-10 production was restricted to this CD1d(hi)CD5(+) B cell subset, with IL-10 production diminished in Cd19(-/-) mice, yet increased in hCD19Tg mice. Thereby, CD1d(hi)CD5(+) B cells represent a unique subset of potent regulatory B cells.

  • FDA Refuses to File Celgene Application for MS Candidate Ozanimod

    Celgene has acknowledged that the FDA sent the company a “Refuse to File” letter in response to its New Drug Application (NDA) for the relapsing multiple sclerosis (MS) candidate ozanimod—the biotech’s second setback to one of its later-stage drug candidates in recent months.


  • Interesting study (profGs twitter)

    We show that preventive application of nimodipine (10 mg/kg per day) starting on the day of induction had ameliorating effects on EAE in SJL/J mice immunized with encephalitic myelin peptide PLP139-151 , specifically in late-stage disease. Furthermore, supporting these data, administration of nimodipine to MOG35-55 -immunized C57BL/6 mice starting at the peak of pre-established disease, also led to a significant decrease in disease score, indicating a protective effect on secondary CNS damage. Histological analysis confirmed that nimodipine attenuated demyelination, axonal loss and pathological axonal β-APP accumulation in cerebellum and spinal cord in the
    chronic phase of disease.


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