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MouseDoctor

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  • So, today is a landmark for the fact that cannabis is now prescribable in the UK which we mouse doctors are justly proud of as we were the first to provide definitive evidence of efficacy nearly 20 years ago (where did the time go?).
    However for pwMS it appears that celebrations should be put on hold according to this story. Shameful. Looks like we're going to have to keep pushing.
    https://www.thetimes.co.uk/edition/news/doctors-advised-to-refuse-cannabis-for-ms-sufferers-82w7b7b76?fbclid=IwAR2AYoEmgZgxl0JKiscSzz6jRXr7ZmubfpoSaIYBXralFDbG_Vnx1ZidNgQ

  • How about the mouse doctors come up with an inducible model of myelin degeneration and inflammation that doesn't rely upon massive injections of mog peptide?

    Can the mouse doctors test some of the rhoA and rock inhibitors on these mice?

    Has eae research tainted the field of Ms research because of the heavy reliance on immunization to break up the BBB and flood the short time frame of disease?

    Is there a better animal model that can have relapsing disease like guinea pigs and hsv1 (for example)?

    • Inducible model of myelin degeneration…they have already made some that get myelin degeneration but the problem with mice is that you remove myelin and the nerves die.

      We use the ABH and dont use MOG peptide:-)

      You can use cells transfer or transgenics that mean no immunization.

      We did ROCK and Rho inhibitors on the regular variant about twenty years ago.

      Is there a better model. The guinea pig strain 13 has a relapsing disease and much better histology. However, who has strain 13 guinea pigs? I don't know anybody who has them.

  • Meant to say hsv2…
    Especially with crispr and humanized mice with reconstituted immune systems from rrms spms or ppms immune systems, better models should be being made right now.

    • I agree and spent a year saying this to the progressive alliance, they agreed but nothing happened. In Australian they were making humansized mice, but they ran out of cash, but they mice were not giving reproducible disease and needed more tweaking

    • "In Australian they were making humansized mice"

      Big difference between "humanized mice" and "human sized mice"

      Just one letter.

  • Is there any known connection between retinal disease (parsplanitis, chorioretinitis, intermediate retinitis etc) and MS. May disease affecting the nervous tissue of the eyes precede develop of MS?

  • Miscellaneous news

    -Astrocytes Can Alter Myelin Thickness to Change Neuronal Transmission Speed
    "Researchers found that perinodal astrocytes regulate adhesion molecules that connect myelin to axons. When these molecules are cut by the enzyme thrombin, myelin detaches from the axon, layer by layer."
    http://www.pnas.org/content/early/2018/10/23/1811013115

    -Nature of Immune Cells in Brain Discovered
    Researchers have discovered how the nature of T cells help protect the brain from viruses. The findings shed light on the role the immune system plays in a number of neurodegenerative disorders.
    The scientists have found that the two proteins CTLA-4 and PD-1 are present in large quantities on T cells. These proteins, for which the Nobel Prize for Medicine has been awarded to the discoverers this year, are important inhibitors for T cells.
    doi:10.1038/s41467-018-07053-9

    -Inflammation Can Lead to Circadian Sleep Disorders
    “NFKB alters the core processor through which we tell time, and now we know that it is also critical in linking inflammation to rest-activity patterns”
    doi:10.1101/gad.319228.118

    -Enzyme that triggers autoimmune responses from T-cells in patients with MS found
    DOI: 10.1126/scitranslmed.aat4301

    -Denali Therapeutics will work with Sanofi on its multiple RIPK1 inhibitor molecules that could treat a range of neurological and systemic inflammatory diseases.
    two lead molecules DNL747 and DNL758 target a critical signaling protein known as the receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in the TNF receptor pathway, which regulates inflammation and cell death in tissues throughout the body. As Denali pointed out, the two companies plan to study DNL747 in Alzheimer’s disease, amyotrophic lateral sclerosis and multiple sclerosis, and DNL758 in systemic inflammatory diseases such as rheumatoid arthritis and psoriasis.

    -National MS Society Invests in Clinical Development of Human Antibody for Progressive Forms of MS
    Fast Forward, a nonprofit subsidiary of the National Multiple Sclerosis Society, will invest up to $330,000 to advance the clinical development of an antibody that was shown to lessen inflammation and nerve cell damage in a multiple sclerosis (MS) mouse model.
    https://multiplesclerosisnewstoday.com/2018/10/31/national-ms-society-invests-clinical-development-potential-therapy/

    -Blocking Molecule Evident in Excess in MS Patients Treats Mice with SPMS-like Disease, Study Reports
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193044/

    -Inhibition of the SARM1 gene can prevent the degeneration of nerve cells in the central, ocular, and peripheral nervous system in mice, results from preclinical studies show.
    These findings provide evidence for the use of small-molecule inhibitors of the SARM1 protein being developed by Disarm Therapeutics as potential disease-modifying therapeutics for several disorders, including multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), glaucoma, and peripheral neuropathies.
    https://bionewsfeeds.com/2018/11/08/sarm1-inhibition-has-potential-to-prevent-neurodegeneration-in-als-other-diseases-preclinical-results-suggest/?fbclid=IwAR2KbNx5FnZJQ0vcv66MR6D_WaQJWsnABxYpzGawenDRlolK_9nwSIdoq48

  • Are you ppms?

    Do you have relapses?

    If so, thats a "good" thing (prognostic)

    Association of Inflammation and Disability Accrual in Patients With Progressive-Onset Multiple Sclerosis

    In this longitudinal, prospective cohort study of 1419 patients with progressive-onset multiple sclerosis, superimposed relapse was associated with a reduced likelihood of confirmed disability progression. Time spent on disease-modifying therapy reduced the likelihood of progression in progressive-onset patients with relapse but not in those without relapse

    https://jamanetwork.com/journals/jamaneurology/fullarticle/2694820?guestAccessKey=fe20d8e6-8b32-4f31-b67e-dfb88199687c&utm_source=silverchair&utm_medium=email&utm_campaign=article_alert-jamaneurology&utm_content=etoc&utm_term=111218

    Obrigado

  • Fasting, exercise or ketogenic diet is good for pwms

    The b-hydroxybutyrate receptor HCA2 activates
    a neuroprotective subset of macrophages

    DOI: 10.1038/ncomms4944

    Obrigado

  • Ocrevus Helps Preserve Hand and Arm Function in PPMS Patients, Trial Data Show.
    (MS News Today).
    Will the NICE reconsider DMT for Advanced MS?

  • Caroline Wyatt's HSCT did not work so get prepared for a new wave of disbelief for the treatment, as she is the only patient whose expreriences are not anecdotal.

    • I think you will find that she tried to get this treatment on NHS but was turned down as i guess not a good candidate for response and so went to Mexico. Therefore limited to no response was to be anticipated, I suspect that this decision was taken too late as it so often is. A treatment of last resort when the nerve reserve has been exhaused by infective first line DMT.

    • Symptoms in 1992..Diagnosed RR in 2015..what a disaster.
      My pediatrician diagnosed me over the phone by symptoms alone
      and this was 5 or 6 years before hospital even had a MRI. Thatcher
      and Reagan were still in office for goodness sake.

      She tried to get in at Sheffield but was denied since MRI showed
      no "active or inflammatory lesions in the brain" So now she's
      SPMS and no treatment that can stop the neurodegeneration. If
      HSTC could do it they would give to ALS and ALZ patients.

  • "myelination in the cortex is a lifelong
    process"

    Seeing Is Believing:
    Myelin Dynamics in the Adult CNS

    Live imaging studies in mice showthat adult-born oligodendrocytes and myelin are remarkably stable. Neural
    activity enhances oligodendrocyte integration, arguing that internode addition rather than alteration represents
    the mechanism for any experience-dependent cortical myelination changes that might underpin
    learning.

    Together, these beautifully executed
    live imaging studies demonstrate clearly
    that myelination in the cortex is a lifelong
    process (Figure 1). New oligodendrocytes
    are formed continuously and either die
    or integrate, producing new internodes.
    Integration is enhanced by neural activity.
    Once formed, and irrespective of time of
    differentiation, cortical oligodendrocytes
    and their internodes are remarkably stable

    https://www.cell.com/neuron/fulltext/S0896-6273(18)30377-5

    Finally, the live imaging studies also
    have interesting implications for understanding
    neurodevelopmental diseases
    that impact cognitive function. The role
    of cortical myelination in disease has,
    apart from the recognition of demyelinating
    lesions within gray matter in multiple
    sclerosis, received little attention. The
    stability of cortical internodes, taken in
    conjunction with the observation that individual
    oligodendrocytes form their internodes
    within a few hours, suggests that
    variations in the size and number of internodes
    formed by an oligodendrocyte will
    be lifelong. It follows that any perturbations
    in myelination, such as those that
    might result from transient exposure to
    environmental toxins, i.e., drugs, from
    trauma or infection could, as a result of
    abnormally placed or formed internodes,
    alter circuit behavior and cognitive function
    permanently. Although speculative,
    such a conclusion emphasizes the power
    of these live imaging studies in forcing
    new thinking about the contribution of
    oligodendrocytes to brain disorders

  • One for the "Black Swan" 🙂

    Although there is no medical evidence that HIV or AIDS causes Alzheimer's disease, existing FDA-approved antiretroviral therapies for HIV that block reverse transcriptase might also be able to halt the recombination process and could be explored as a new treatment for Alzheimer's disease. The scientists noted the relative absence of proven Alzheimer's disease in aging HIV patients on antiretroviral medication, supporting this possibility.

    "Our findings provide a scientific rationale for immediate clinical evaluation of HIV antiretroviral therapies in people with Alzheimer's disease," says Chun. "Such studies may also be valuable for high-risk populations, such as people with rare genetic forms of Alzheimer's disease."

    https://medicalxpress.com/news/2018-11-never-before-seen-dna-recombination-brain-linked.html

    Obrigado

    • Can't quite believe it's a year luis since some of us were wishing you well with the treatment!
      I might say Happy Anniversay instead of birthday, but either way, I hope that you've benefitted from receiving stem cells and that, as someone who makes a lot of valuable contributions to the Blog, you continue to do well.

    • Luis..why did you do it ?..do you think it will change permanently
      your immuno CSF brain environment so nuerodegeneration will not happpen..?

    • We are all TRYING to buy MORE time

      Thats why i did it

      To buy more time

      How much?

      I wish i have the answer

      Thanks to all
      Obrigado

  • Do pwMS use D-Mannose for UTI's? Does it work long term?

    I found the following study on the web.
    D-MANNOSE to prevent UIT's in MS patients. Panicker, Chataway et al (2016).

    Conclusion – The use of D-mannose in MS patients reporting recurrent UTIs is associated with a reduction in the number of UTIs and antibiotic prescriptions, without safety concerns. Larger studies are required to confirm efficacy.

    I get recurrent UTI's. thanks.

    • When this was first reported it, it was pregnant cats, if they irradiated the food the cats demyelinated. UCk set of experiments

  • I see aspirin more as a downregulator of hot microglia rather than an immune modulator per se. Trouble is who would fund a clinical trial as there's no money to be made out of aspirin?

    • Do you personally think MD2 that hot microglia leads to neurodegeneration or a progressive MS state, in addition to demyelination?

      Do you think hot microglia is the APC in MS?

  • Please can someone please point me in right direction for prof g recommendation for vitamin d. I bought my daughter 5000iu. She does not have MS and I want yo make sure this is safe. Thanks

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