May Q & A 2019

M

For those questions that don’t fit with the posts and other queries

Iris Anvil of Darkness

About the author

MouseDoctor2

148 comments

  • Does Ocrelizumab cause long term irreversible immune suppression?

    If so: from the outset or after X number of infusions.

  • I have a neurology appointment tomorrow to discuss therapy for RRMS. It seems like there is no easy option around choice of DMD. Please can you help me in terms of any kind of thought process I can use? Thank you. I think your blog is brill.

  • What is the latest information concerning Ocrelizumab and Primary Progressive MS Patients. ? We seem to be waiting so long for any treatment.

    • Roche and NHSE and NICE are still in negotiation mode! Let’s hope we hear soon. We were expecting news several weeks ago.

      • The news that ocrelizumab has been approved for primary progressive MS is being hailed a major success but the NICE guidelines are really restrictive so they don’t really want to approve it do they?

  • Is this HERV-W treatment somehow wandering under the MS Blog radar towards Phase III Studies? Any comments at this point? Still the proverbial “Black Swan”?

    http://www.geneuro.com/data/news/GeNeuro-PR-ANGEL-MS-EN-VF.pdf

    ANGEL-MS Phase 2b extension study confirms and extends the neuroprotective effects of temelimab in MS

    GeNeuro, a biopharmaceutical company developing new treatments for neurodegenerative and autoimmune diseases such as multiple sclerosis (MS), has announced positive results from the ANGEL-MS study of its lead product, temelimab in MS.

    Temelimab is a humanised, monoclonal antibody designed to neutralize pHERV-W, a pathogenic protein thought to be a causal factor in the development of MS.

    The ANGEL-MS data confirmed that treatment with temelimab for two years had a continued, positive impact on key MRI measures of disease progression in MS patients, confirming and extending the data reported at Week 48 in the CHANGE-MS Phase 2b study. This includes reductions in brain atrophy, particularly in the cortex and thalamus, and maintenance in myelin integrity, as measured by magnetization transfer ratio (MTR) imaging. Importantly, for the first time, encouraging dose-dependent effects were seen on clinical measures of disease progression. This has been evidenced by a lower proportion of patients with 12-week confirmed EDSS progression, or with 20% worsening in 25-foot timed walk

  • Hoping to hear very soon about the potential ‘add-on’ and neuroprotective drug trial that Prog G mentioned a few weeks ago, using a Myeloma drug, if I remember correctly. Any further news on this please?

    • Bortezomib-side-effects
      More Common

      Black, tarry stools
      bleeding gums
      blood in the urine or stools
      blurred vision
      body aches or pain
      burning, crawling, itching, numbness, prickling, “pins and needles”, or tingling feelings
      chest pain
      chills
      confusion
      cough
      cough producing mucus
      decreased urination
      difficult or labored breathing
      dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
      dry mouth
      ear congestion
      fainting
      fever
      headache
      increase in heart rate
      loss of voice
      lower back or side pain
      nerve pain
      painful blisters on the trunk of the body
      painful or difficult urination
      pale skin
      pinpoint red spots on the skin
      rapid breathing
      runny nose
      sneezing
      sore throat
      stuffy nose
      sunken eyes
      sweating
      swollen glands
      thirst
      tightness in the chest
      troubled breathing with exertion
      ulcers, sores, or white spots in the mouth
      unsteadiness or awkwardness
      unusual bleeding or bruising
      unusual tiredness or weakness
      weakness in the arms, hands, legs, or feet
      wrinkled skin

      https://www.drugs.com/sfx/bortezomib-side-effects.html

      • Do you understand how these lists are required to be compiled?

        Every single thing that a patient reports during a trial makes it onto there.

        Frequency and severity are key. Deaths from all other causes are recorded. You gotta dig into the data, if the drug company accede to requests for it that is.

        Have you ever been a patient in a trial or been involved in running one? Just curious. They are odd things.

  • Good news for people with Parkinson’s disease recently concerning an implant boosting nerve signals back to the brain helping patients walk normally. Is there any chance this or similar technologies could work for PWMS, boosting signals deduced through demyelination or lesions?

  • Selma Blair is using plasma exchange to help with her MS. She further says its helped her immensely with her MS. Any views or thought on this therapy working? If it works why isn’t it offered in UK?

  • Patients are paying up to 20 times more for neurological drugs since 2004, study finds

    The study, published Wednesday in the journal Neurology, found that the average out-of-pocket costs for people taking medications for multiple sclerosis had risen the greatest over the past 12 years, costing 20 times more in 2016 than in 2004
    Using a large health care claims database, researchers examined out-of-pocket costs for more than 912,000 Americans with dementia, epilepsy, multiple sclerosis, peripheral neurophathy or Parkison’s disease over 12 years. These patients were privately insured and took at least one neurologic medication. Out-of-pocket costs were up for each disorder, but MS patients have seen the sharpest rise.
    “It is likely out-of-pocket costs will continue to increase,” Callaghan said.
    https://edition.cnn.com/2019/05/01/health/neurology-drug-prices-study/index.html?fbclid=IwAR3v-8Pggm4NkkUfYR5Hz-UEpanXpfbo9_06MV5KWcQJxI0jJGndoeVkS2Q

    Out-of-pocket costs are on the rise for commonly prescribed neurologic medications
    https://n.neurology.org/content/early/2019/05/01/WNL.0000000000007564

    Where is MD to tell us that Gilenya had to be expensive because pharma needed money for reasearch to create Mayzent (same applies to all new MS drugs) ?

    • I am not going to say anything in support of the pricing structure, it is clear the price has nothing to do with trial costs or manufacture costs, it is what the Americans are willing to pay how can copaxone cost what it does and the price inflation is riduiculous.

      However some of the trial costs are staggering

  • Evaluating Use and Impact of High-Efficacy Multiple Sclerosis Treatments

    “Higher efficacy therapies appear to have a disproportionately larger effect on younger patients,” the researchers concluded.
    https://www.ajmc.com/newsroom/evaluating-use-and-impact-of-highefficacy-multiple-sclerosis-treatments?utm_source=dlvr.it&utm_medium=facebook

    Monoclonal Antibody Therapy and Long-term Outcomes in Multiple Sclerosis – The Challenge of Treatment Optimisation
    https://touchneurology.com/monoclonal-antibody-therapy-and-long-term-outcomes-in-multiple-sclerosis-the-challenge-of-treatment-optimisation/

    • Have I seen ths
      Antidrug Antibodies Have Minimal Impact on the Pharmacodynamic Profile and Clinical Efficacy of Alemtuzumab in RRMS Patients From the CARE-MS Studies Tjalf Ziemssen, Antonio Bertolotto, Samuel F Hunter, Jan Lycke, Alan Jacobs, Luke Chung, Qifeng Yu, Isabel Firmino, Christopher LaGanke, AAN 2019

      Not yet but ProfG & DrK please get the QR code so I get a copy.

      Have I seen this.
      P611 – Minimal impact of anti-alemtuzumab antibodies on the pharmacodynamics and efficacy of alemtuzumab in RRMS patients from the CARE-MS studies A. Jacobs, L. Chung, Q. Yu, I. Firmino

      Yes…at ECTRIMS2018 but the difference is the author list. It seems that the work has collected a few academic coat tail hangers. If they were involved in the work surely they would have been on the ECTRIMS poster?

      Is this the way you buy silence after all if we go back to ECTRIMS2017 and ask have we seen this

      P1231 – Abrogation of the lymphocyte depleting action of Alemtuzumab by neutralizing antibodies – a case report
      C. Eggers, K. Akgün, T. Hofer, M. Egger, T. Ziemssen (http://www.professionalabstracts.com/ectrims2017/iplanner/#/grid)
      should we look at the disclaimers

      C. Eggers received speakers fees and honoraria from Sanofi-Genzyme, Teva, Merck-Serono, Biogen-Idec and Novartis.
      K. Thomas has nothing to declare, T. Hofer has nothing to declare, M. Egger has nothing to declare, T. Ziemssen received speakers fees and honoraria from Sanofi-Genzyme, Teva, Biogen-Idec and Novartis.

      You can find the poster (Online) it even thanks DrK..Why has it not been published we know there was a plan to do this

      You could even ask Have I seen this
      Kousin-Ezewu O, Azzopardi L, Parker RA, Tuohy O, Compston A, Coles A, Jones J. Accelerated lymphocyte recovery after alemtuzumab does not predict multiple sclerosis activity. Neurology. 2014 Jun 17;82(24):2158-64.

      Yes. It and all the above say that most people deplete after the thrid or more cycle of alemtuzumab. Dr Coles showed this 5 years or more ago so what new.

      (a) The EMA have approved the third dose for treatment failures and
      (b) It is more evidence to try and discredit the suggestions made in Baker et al 2017. There it was suggested that anti-drug antibodies would be important to some people who need a third or more course.

      Now I have not seen the poster you mention yet but it will show that people deplete after 3 or more cycles, but it I suspect with not address the specific questions posed to Genzyme many years ago, which this data i suspect will not address. So go on Tjalf Ziemssen, Antonio Bertolotto, Samuel F Hunter, Jan Lycke, and Christopher LaGanke grow some balls and get this paper published and please, please god, let me be the one to review it.
      The evasion simply suggests something is being hidden and you make people dig and when people dig they find dirt and remember you find dirt in a mole hill, why have you made it a mountain?.
      Surely ECTRIMS and AAN should stop pretending. They are a big meeting because pharma was sending Neuros to the meeting to learn. The meeting organisers are happy because they are getting loads of money from the registrations and pharma for hosting the stands. It is after all a trade show. The powers that be then said pharma can’t support you to come to a meeting unless you are presenting so now we have this nonsense whereby Pharma write and make the poster and do the work and then add a load of free-loading people onto the poster. How many Posters are ProfG, DrK on? It is the way of the world but let’s not pretend about these things
      Anyway rant over, but it reminds me of an Axyl Rose monologue on GnR “civil war” :-).

      All I can say is keep up the subterfuge we all like a good conspiracy theory and it gives my students projects and me papers. You never know maybe I will be on the gravy train one day…let’s live in hope…Maybe I say too much that’s my problem

  • It’s been a few months since I logged onto this blog. What happened to thus site? It is so disorienting now. Previously, I was able go get great information from this blog. Now, I don’t know where to look. Ugh.

    • There you go..move platforms nice and easy blogger, and then wordpress much better search function but thats it as far are ease goes so think how I feel

  • AAN 2019

    When you dig you find that things get more and more complicated

    Aparently IgG1 antibodies from ms are pathogenic when they are intrathecal infused in mice

    But ONLY those for PPms not RRms

    Once again one disease 2 responses

    Ok this is my speculation epitope spreding should take into acount

    If you accept that then could be one disease are all

    🙂

    Intrathecal Injections of
    Primary Progressive Multiple Sclerosis Derived Antibodies
    Result in Motor Deficits and CNS Pathol
    ogy in Mice Suggesting Leading Role of
    Antibodies in CSF Effects

    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-003171.pdf

    • DActualluy profG has been following the story and the anti-viral effect, but if the effect is to get rid of virus in the brain, in my mind it is D”izzie Rascal Song” as so little antibody gets in the brain

  • AAn 2019

    Treatment with oral ibudilast slows brain shrinkage in patients with primary progressive multiple sclerosis (PPMS), but not in those with secondary progressive MS (SPMS), according to results of a Phase 2b clinical trial
    https://multiplesclerosisnewstoday.com/2019/04/04/aan2019-ibudilast-slows-brain-atrophy-ppms-phase-2b-trial/?utm_source=Multiple+Sclerosis&utm_campaign=1d0dae1f28-RSS_NON-US_EMAIL_CAMPAIGN&utm_medium=email&utm_term=0_b5fb7a3dae-1d0dae1f28-71699829

    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-002237.pdf

    One disease 2 responses.

    🙁

    • I posted on this report about 3 weeks ago….you can only get a positive if the control group deteriorate. If neuros do not learn this they will doom more treatments to failure.

      • Yep sorry

        I remember now 🙂

        Just finished read all 463 abstrats in the Aan 2019 website

        So i am a bit brain drain (even more)

        🙂

        • Apparently effect on brain volume and not on disability did they thinkhand what does it mean for the future of ibudilast phase 3 needs a clinical outcome

    • Thanks i missed this one hope profg gets the poster.. we asked for the memory B cell data two years ago now they say no link. Thats fine but i am not sure it is the way i would approach it.

        • The r values are rubbish 0.3 is next to meaningless even if it is statistically significant. Nothing is bigger than r 0.6

          • MD, you’re the expert. I am a bit confused and fear this may be above my pay grade.

            R is a measure of correlation, -1, 0 or +1 if memory serves?

            P is significance, 0.05 and smaller is considered to show significance.

            I was a Stata baby. Do you mean R as in the program?

          • r = spearmans rank correlation coeifcient a stats test. There is a blog post on this. r = 0 is unrelated r =1 postive correlation as one parmater goes up so does the other, r= -1 a negative correlation as one goes up the other goes down r= less than 0.6 is meaning drivel that says nothing about what will happen to the individual but creates paper fodder that litters clinical research. The MRI field is full of this as a consequence we have no real clue what it really measures most of the time

  • Selected Pipeline and treatments

    Bile Acid Metabolism is Altered in Multiple Sclerosis and Supplementation Leads to Amelioration of Neuroinflammation
    Conclusions:BA metabolism was altered in both adult and pediatric MS. BA supplementation ameliorated EAE and in vitrotreatment prevented pro-inflammatory polarization of microglia and astrocytes.
    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-002508.pdf

    Immune tolerance in patients with Multiple Sclerosis and Neuromyelitis Optica by peptide-loaded tolerogenic dendritic cells: final results of the phase 1b clinical trial and extension
    Conclusions:The intravenous administration of peptide-loaded DCs vaccination is safe, feasible and effective in eliciting antigen specific IL-10 production by T regulatory cells in MS and NMOSD patients.
    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-002508.pdf

    A Phase 1, Multiple-dose Study of Elezanumab (ABT-555) in Patients with Relapsing Forms of Multiple Sclerosis
    Elezanumab is a fully humanized monoclonal antibody directed against repulsive guidance molecule A (RGMa). Studies in patients with multiple sclerosis (MS) demonstrate RGMa upregulation, which inhibits axonal growth and myelination, oligodendroglial regeneration and functional recovery after trauma or inflammation.
    Conclusions:Elezanumab was well-tolerated and did not consistently result in symptom worsening in patients who received multiple doses of up to 1800 mg. Additional long-term studies are required to elucidate elezanumab efficacy in a more robust patient population
    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-002725.pdf

    A Phase 1b, open-label study to evaluate the safety and tolerability of the putative remyelinating agent, liothyronine, in individuals with multiple sclerosis
    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-004059.pdf

    Phase 2 AFFINITY Trial Evaluates Opicinumab in a Targeted Population of Patients With Relapsing Multiple Sclerosis: Rationale, Design and Baseline Characteristics
    (ProfG is in this one)
    Conclusions: AFFINITY is investigating the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory DMTs in a subpopulation of patients with MS with potentially enhanced responses to opicinumab.
    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-001625.pdf

  • Hello. Happy month of May everyone!
    My question: I’ve been on tecfidera for 3 years but had two relapses at the end of last year so am no longer benefiting from it. I’m still taking it as I am on a six month (sigh) waiting list for ocrevus… anyway, while on tecfidera I had noticed very bad hair loss. In the last few months this has no longer been an issue. I wanted to ask is there a relationship? Could it be that my hair loss is improving because tecfidera is no longer working for me? Thanks.

    • You do need a trial, we know about the potential effects of proteosome inhibiotrs, but you also need to know that these agents do not come without side effects. Only last week we had people saying proteosome activators are what you need and there are side effects with bortezomib including neuropathy. We are planning on using a second generation molecule with a better side effect profile.

  • Did anyone listen to the Radio 4 programme yesterday at 9pm? Called ‘The great science publishing scandal’.
    It was about who owns research. Scientists, publishers or the public? Includes how this impacts on neurological/ medical societies. It’s on BBC Sounds to listen to.

    https://www.bbc.co.uk/sounds/play/m0004l7k

    P.S You don’t need a TV licence to use BBC Sounds or BBC iPlayer Radio. The law applies to watching and downloading TV programmes, including via BBC iPlayer. (BBC website)

    • This is an ongoing debate, for sure. To listen to BBC you do need to be coming through a UK server. VPN spoofing ought to make this easy. Just saying 😉

      • This was a foreseeable mess that well meaning academics created. The publishing houses are laughing all the way to the bank and now i have to delete fifty requests a week of rubbish journals asking me to pay for the pleasure of publishing. The system is broken. They want about £1500-3500 + VAT for the pleasure. We do the work, we review the papers for nothing, the library pays crazy prices to buy access, and then you via the governments pay to have it made public. Is this why you do marathons and all sorts of good deeds to throw money away? Charities demand that work is open access but refuse to pay for it. It is senseless use of public funds. The UK government should set up a publishing house, core fund it and get rid tof he impact factor nonsense that we are trapped in.

  • Does benign MS actually. If so what is the definition? Anyone who can’t feel theiregs as a relapse in my opinion does not have benign ms regardless of lack of disability after 15 years. Any views?

  • If you were instructed to stop Gilenya for an exceedingly and consistently low lymphocyte count, would this low count negate the possibility of rebound activity?

  • One of the strangest abstract in this AAn 2019

    Was this

    A Case of Multiple Cocaine-Induced Toxicities: Rash, Neuroleptic Malignant Syndrome,
    and Levamisole-Induced
    Leukoencephalopathy

    http://indexsmart.mirasmart.com/AAN2019/PDFfiles/AAN2019-001687.pdf

    Basicaly a 30-year-old male cocaine user had some type of brain inflamation due to the the drug being contaminated with Levamisole ( anti-helminthic agent, found in up to 80% of cocaine as a diluent)

    Beware of what´s in the drugs you are taking

    😉

  • BBC Radio 4 Today just reported that NICE and Roche have agreed terms and Ocrelizumab (Ocrevus) has been approved for use in PPMS.

  • Ocrelizumab now approved for ppms. Great news for every MS patient. Just being on treatment will increase a patients well being. NHS is truly a jewel in the crown.

    • “Just being on treatment will increase a patients well being.”

      I don’t follow that. A treatment has to work, and not have nasty side effects.

      Ocrelizumab is not available for all presentations of PPMS.

      • Many pwMS appreciate the extra attention they get from medical professionals on a clinical trial even if on placebo in the past.

        • This is a very valid point. I am in my 2nd year of Cladribine treatment and have not seen my consultant for well over 12 months now; struggling not to worry about continued worsening. I miss his advice and support and sympathise with MS nurse who has way too much to deal with. I rely on this blog for advice and have learnt so much about MS and treatments – thankyou to all who contribute at Barts.

  • The news that ocrelizumab has been approved for primary progressive MS is being hailed a major success but the NICE guidelines are really restrictive so they don’t really want to approve it do they?

    • It is a price restricting institution and so they restrict access to those most likely to response, will they do studies with cladribine and alemtuzumab? It may depend on the patent situations but I suspect the time has past and not enough time to do studies and reap the reward so the makers of ocrelizumab (Roche & Biogen) laugh all the way to the bank……perhaps until some side effect pops up.

      • If a patient fails Alemtuzumab. Where does a patient go? For instance is HSCT a option? Given Alem is HSTC in a bottle what chances are there for HSCT to work if you fail alem? Or is that the dead end of treaent?

        • Alemtuzumab is not HSCT in a bottle, it is more selective, with lower success rates, partly due to drug antibodies (as MD supports). If you have failed Alem. because you are PMS, HSCT might not help either. Otherwise, it most certainly will.

          • Thanks anon for your reply. I havnt yet failed alem. And not Ppms. Just thinking if there’s alternative to alem out there that is either approved or not. HSCT is still too risky. But will consider it if I fail alem. Unless there’s a alternative out there such as using crisp etc.

      • As a pwMS on Ocrelizumab, you’ll forgive me if I don’t share in your schadenfreude should a ghastly side-effect pops up.

  • Can anyone recommend a genuine and affordable seller from whom I can buy Alpha Lipoic Acid 600mg capsules?

      • Thanks for the heads up Luis, but having checked their ALA supplement is hellish expensive.
        Think I’m correct in saying that Rebecca Spain is now conducting research into which is the most effective stabilised R-lipoic Acid or the synthesised version – so I’m taking both at the moment, though still not as high a dosage as used in her study with SPMS.

  • Very interesting

    New research identifies that microglia play a vital role in regulating neuroinflammation in autoimmune disease, which may one day lead to treatment targets for the retina disease, uveitis.

    In a report published online in Proceedings of the National Academy of Sciences (PNAS), the researchers describe, for the first time, a role for microglia in directing the initiation of autoimmune uveitis by orchestrating the inflammatory response within the retina. In reaction to disease induction, microglia closely associate with the retinal vasculature and facilitate inflammatory immune cell entry past the blood brain, or ocular, barrier into the retina. When the researchers depleted microglia in this model, they observed that the disease was completely blocked.

    “Normally, the blood brain barrier serves as an impediment and prevents the immune response from going into tissues of the central nervous system, including the retina. However, our results provide clear evidence, that in the context of uveitis, microglia can facilitate entry of inflammatory immune cells into the retina, and enable the host immune responses to attack cells that are not normally recognized by the immune system,” said senior author Kip M. Connor,

    https://www.technologynetworks.com/neuroscience/news/microglia-limit-photoreceptor-damage-in-sight-threatening-model-318462?fbclid=IwAR0YwfvYt0SRD1bd6hsc6l4a1lUP3iIJprHMaq0Aj3SvgNr9Uvo-fiEdVOI

  • The neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios are independently associated with neurological disability and brain atrophy in multiple sclerosis

    Results: Unadjusted analyses demonstrated significant associations between higher NLR (but not MLR) and PRO measures including greater depression (p= 0.01), fatigue (p<0.01), and decreased physical quality of life (p<0.01). Higher NLR/MLR were both strongly associated with increased MS-related disability as assessed by the Expanded Disability Status Scale, independent of demographic, clinical, treatment-related, neuroimaging, and psychosocial variables (p<0.001 for both). Lastly, higher NLR/MLR significantly discriminated progressive from relapsing status (p≤0.01), and higher MLR was associated with increased whole-brain atrophy (p<0.05) even after controlling for all clinical and demographic covariates. Sensitivity analyses using the subset of untreated patients (N=146) corroborated these results.
    Conclusions:Elevated NLR/MLR may represent markers for pro-inflammatory priming of the myeloid innate immune system (numerator) in conjunction with dysregulated adaptive processes (denominator), and consequently reflect severity of MS-related neurological disability and radiological outcomes.

  • More 🙂

    Statins

    Atorvastatin Associated With Milder Disease Progression in Relapsing-Remitting Multiple Sclerosis

    Results

    After 8.4 ± 2.3 (3.7–11.9) years from trial, the use of atorvastatin was associated with reduced risk of 1-point EDSS progression (HR = 0.440; 95%CI = 0.225–0.861; p = 0.017), and of EDSS 4.0 (HR = 0.310; 95%CI = 0.123–0.784; p = 0.013). We found no significant association between atorvastatin and relapse

    After 8.4 ± 2.3 (3.7–11.9) years from trial, the use of atorvastatin was associated with reduced risk of 1-point EDSS progression

    This is nice taking the fact that patients where taking interferon

    🙂

    • Luis, did you do a fast mimicking diet or you went food free all those hours? Have you ever tried a water fasting? Amazing effort!! It would be nice to see your research on fasting gathered in a blog or fb page…

      • 🙂
        I eat normally in an 6 /8 hour window frame

        (start eating at 13h until 20h next day the same)

        Thursday and sunday i only eat 600 calories in one meal

        3 times a year i do this crazy s%%%55ªªº$$%%%&&6###%%%t

        Where i fast for 4 days (almost) 🙂

        I drink only water or cofee or tea

        I tend to loose 3 kg blood sugar level drop to 49 colesterol raises a bit

        Your brain is on fire 🙂

        Look at min: 59:15 (Would advise to it the whole story)

        https://youtu.be/Gm626MgpveI

        I am not alone:)

        Obrigado

  • New
    Cellular Stress, Not Infection, May Rouse Slumbering MS-Linked Retroviruses

    One possibility, suggested by several recent studies, is that human endogenous retroviruses (HERVs) are activated by infectious phenomena. Another possibility is that HERVs become active when cellular stress causes inflammatory responses to become dysregulated. This second possibility has just been proposed by scientists based at the Institut Pasteur.
    https://www.genengnews.com/news/stress-not-infection-may-rouse-slumbering-ms-linked-retroviruses/?fbclid=IwAR0VMLRlpqbARYLjmduJvyB9-1y0WUa9GGmpv5qE8N1O6BgalGoWeX9NlIo

    Expression of endogenous retroviruses reflects increased usage of atypical enhancers in T cells
    http://emboj.embopress.org/content/early/2019/05/08/embj.2018101107

  • Opioids are helpful only for one in ten people. According to Radio 4 programme today on opiods.

    Is this a similar figure for pwMS?

  • Time Is Brain and Spine

    To the Editor I read with interest the article by van der Vuurst de Vries et al.1 The authors concluded that the clinical application of the revised 2017 McDonald criteria2 would result in the diagnosis of multiple sclerosis (MS) in more patients with a projected less active disease over 5 years.1 I would like to highlight that the natural history of MS has evolved into a disease with overall lesser morbidity and disability.3 The favorable outcomes are partially due to earlier diagnosis and treatment.3 The recent revisions of the McDonald criteria aimed to provide the clinician with the ability to diagnose MS at an earlier stage, allowing for prompt commencement of the disease-modifying therapy. van der Vuurst de Vries and colleagues1 confirmed the substantial increase in sensitivity when applying the 2017 criteria. However, they were critical of the observed decrease in the specificity for MS diagnosis compared with the 2010 McDonald criteria at a mean follow-up of 5 years. As noted in their article’s Limitations section, a duration of 5 years might not be sufficient, especially considering that the 2017 revisions allowed for earlier diagnosis. Longer follow-up periods are necessary to provide accurate conclusions about the specificity of the revised criteria. The figure of survival curves provided by the authors highlighted an expected trend.1 The longer the duration of follow-up was, the stronger was the agreement between the 2017 criteria, 2010 criteria, and clinically definite MS. This observation calls for studies with longer durations to generate a more relevant specificity data of the revised 2017 criteria. The new criteria are still in their infancy and they need to be validated for longer follow-up periods and in diverse patient populations. Finally, earlier diagnosis and treatment of MS matters, as time is brain and spine.

  • Time Is Brain and Spine—Reply

    In Reply We agree with Obeidat that the overall prognosis for patients with multiple sclerosis (MS) is getting better. This is partly because of earlier treatment with disease-modifying therapies (DMT), but it is also due to changes in the MS criteria over time; the consecutive criteria for MS have gradually become less strict and have led to a better prognosis in the total group of patients with MS.1

    We do not claim that the patients who did not have a second attack in our study will remain monophasic for the rest of their lives. However, what we did observe is that the McDonald 2017 criteria2 created a group of patients with MS with a less active disease course at least in the 5 years after the first attack.1 The question is, should we treat this subgroup with no or hardly active disease in this early stage? There is a trend in starting DMT as early as possible. However, subgroup analyses in clinical trials show that DMT has the best effect in patients with most active disease at inclusion.3-6

    For subgroups with very little disease activity, it can be hard to prove a clinical meaningful treatment effect. Therefore, it is not easy to say that proven beneficial effects of starting early DMT can be extrapolated to the nonactive MS group.

    Diagnostic criteria should discriminate between patients who should be treated immediately because of an expected active disease course and patients for whom we can wait because of an expected benign disease course. Unnecessary treatment in patients with a benign disease course should be avoided. We propose that this aspect should be considered in the next phase of developing criteria for the diagnosis and management of MS.

    Lets wait and see

    🙁

  • A common problem with patients on OCR is that they feel increased levels of fatigue that do not always resolve.
    A solution can be to change to Mavenclad, which seems to have a very positive effect on fatigue.

    A very important aspect when choosing DMT (when you can choose).

      • Just seen it in single doctors practice with patient satisfaction, nothing official or regular. I have seen it too that Mavenclad has gathered many “anecdotal” positive reviews on fatigue, so I assume it has a base.

  • Quick question on barts edss. On this scale I have edss of 1.0 on account of not being able to walk 6km-8km in 2 to 3 hours without rest. My limit is 5. 5 in 1hr 45 mins. On the edss scale at my ms clinic my edss is 0. So why do we have different scales and which one reflects my true edss?

    • I know from posts on this Blog that the team have some strong views of the limitations of the EDSS, especially in regards to upper limb function. Since diagnosis 3 years ago I’ve found it helpful to monitor myself on the scale provided, even though I’m a tad higher on it than the neuro assessment last month. Personally speaking it’s a useful means to where I’m at in terms of progression. It makes me feel more confident of when there’s a genuine need or not to flag things up with my ms nurse. This is alongside following Gavin’s advice to keep a regular record of all symptoms.

      Below is an interesting article again focussing on the limitations of the scale. My thought after reading it was: ‘and it doesn’t include reference to patient anxiety/nervousness!’ I can manage the heel, toe walk quite readily most of the time, but totally failed it when the neuro asked me to do it. I’ve decided from now on my appointments will be accompanied by vids on my phone to evidence what I now know I’m very likely to fail under pressure in the company of a clinician.

      Hope you find this link useful too:
      https://www.everydayhealth.com/multiple-sclerosis/treatment/measuring-multiple-sclerosis-and-disability/

      • Thanks F1. I totally agree with you self monitoring is always best. But just think barts edss is a tad hard for even normal people. Walking to 7 km in 2 to 3 hours is quite challenging. Or has my ms made me forget what it is to be normal?

  • Buy a little help from my friends

    🙂

    Conclusions: Our results supported the hypothesis that the main effect of Cladribine seems to be the selective depletion of B lymphocytes especially Bmem. Moreover, Cladribine could help to restore immunotolerance by increasing Tregs in the early phase of treatment. Further studies with longer follow-up will be necessary to confirm these findings and to define the role of LS as biomarkers of treatment efficacy and safety.

    Changes in Lymphocyte subpopulations in Highly Active Multiple Sclerosis patients during Cladribine treatment.

    https://ipp-ean19.netkey.at/index.php?p=recorddetail&rid=b8b8601b-3892-43fa-a09f-ba935f7a9a8f&t=browsesessions#ipp-record-90262363-4ef3-45f8-a3a7-9cab388f7f23

  • Uau

    A meta-analysis of autologous haematopoietic stem cell transplantation in MS
    G. Mancardi; Genoa/IT
    Abstract

    Abstract:

    Introduction Intense immunosuppression followed by autologous haematopoietic stem cell transplantation (aHSCT) has been evaluated since more than twenty years as a possible therapeutic tool in severe autoimmune disorders. The objective of the presentation is to to evaluate recent published studies and present new unpublished data about the capacity of aHSCT to manage and control severe and treatment refractory MS.

    Methods. We examined the studies on aHSCT utilized in any form of MS reported in the last years. Moreover we collected and evaluated the clinical and MRI outcome in all the patients treated in Italy from 1998 to 2018 in 7 different centers.

    Results The more recent studies confirm the efficacy of aHSCT in abolishing MRI signs of disease activity, reducing realapse-rate and even improving neurological status in patients with aggressive forms of MS. In the Italian experience, at 15 years after aHSCT, almost 60% of 160 evaluated patients did not experience disability progression. This proportion was significantly higher for RRMS (82%) versus SPMS (38%) (p=0.003). At 10 years, 78% of patients was free of inflammatory MRI activity. The proportion of patients free of any disease activity (relapses, inflammatory MRI activity, disability progression) was almost 50% at 10 years. Transplant related mortality was 0.65% (n=1).

    Conclusion All the latest published studies and the large experience gathered in our country demonstrate the extraordinary capacity of aHSCT to impact the disease course of MS. Large phase III studies are running to definitely demonstrate the efficacy of aHSCT in MS.
    Disclosure:
    Nothing to disclose

    https://ipp-ean19.netkey.at/index.php?p=recorddetail&rid=1ae237a5-63e7-46c5-be89-0e4f00fbfaec&t=browsesessions

    • This 38% of SPMS will be excluded from future clinical trials of HSCT, unless they pay for it.
      82% of RRMS is cured but only the lucky ones will get this cure from National Health Care Systems…

  • So we’ve lost ProfG and now I’d really like to know whether we’ve lost Gavin too.
    Please be candid with us and confirm whether you have left the Blog or clarify whether you are only going to submit the occasional post on this site, with the vast majority on other sites such as Twitter ????

    Yes, mine is a loaded question. I think that the example below is just the sort you would have previously supplied on the Blog and those of us who access it for the balance of scientific and patient focussed posts and comments do feel as if we’re now seriously missing out – well, at least I do, especially when you are addressing patient treatment and care and even assisted dying on other platforms.

    Reflections on the ABN 2019…. #PoliticalSpeak “However, the session, or debate, we had on assisted dying was disappointing.” — Gavin Giovannoni

    There is no other site,I’m aware of, quite like this one and therefore I think in the world of MS it is really rather special, even precious. My second question is: if there’s no chance of having you return to the fold then is it possible you can promote with another neurologist taking on the responsibility of providing these vital posts in the accessible and informative style that you do ????

      • But you do not post on medium as regularly as you did on this blog and it is a lot less advisory in relation to current concerns and questions of those with MS

      • Thanks for replying.
        I’d understood the Cry the beloved Country post as being about off-label prescribing, and hadn’t seen it being presented with the covering paragraph about it being moved on to Medium.

        I still find that I’m struggling to grasp the reasons as to exactly why there is value in you posting such critical articles on other sites and not on the Blog.

        After I’d posted my question I realised I’d not completely called it right: not only of benefit to PwMS, but to any clinicians who access the Blog. I’m fond of telling others I think this site should be included in the training of neurologists, due to its aforementioned mix of scientific, patient focussed and comments – definitely pertinent to your post on Information Asymmetry.

        In trying to work through what may have informed this decision, avoidance of getting caught up in time-consuming debate/replies to the comments (such as mine😝) crosses my mind.

        Again, I can’t speak for others, but I’d still prefer to benefit from the Blog readers comments generated by your posts, even if your contributions to the Blog come with the strict proviso that you will be not be participating in the comments section.

        I’d like to ask that you please give it some further thought so that we may continue to benefit from you or a colleague who will address things similarly.

    • Capitalism at its best (or worst), profiteering at all costs. You need to realise that this treatment is probably a cure. Would you pay $2M to be cured of a lethal genetic disease? I suspect you would if you had the money. If this is the case why wouldn’t society also pay £2M? The problem with this argument is that capitalism assumes the pork barrel that funds healthcare innovations is bottomless. It is not; in reality, somebody has to earn and make the money before society can spend it.

  • Guess what lets all eat 65g of red meat everyday

    Why ?
    Its good for ms 🙂

    Gonna show this to the cardiologist 🙂

    The American Heart Association recommends eating no more than 170g per day of animal protein (two 85g servings) – and to opt for chicken, fish or plant proteins (like beans) over red meat as much as possible.

    A Higher Mediterranean Diet Score, Including Unprocessed Red Meat, Is Associated with Reduced Risk of Central Nervous System Demyelination in a Case-Control Study of Australian Adults

    https://medicalxpress.com/news/2019-05-red-meat-healthy-diet-linked.html

    • “Scientists have typically justified excluding female animals from experiments”, not sure this is really a problem in our lab we use what we breed, but mandating use of male and female animals creates issues. If you buy animals from commercial sources then the males will tear each other apart as they have not been weaned in litters. Therefore you have to house them in individual cages. This is not good for social animals. If you group house commercial mice we always buy females.

  • I realise it is now June…

    Regarding clinical trial listings:

    Does clinicaltrials.gov have a comprehensive global reach or does the new UK based NIHR one give a better coverage?

    Thank you.

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