Thursday, 1 November 2018

November Q & A

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14 comments:

  1. 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

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  2. 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)?

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    Replies
    1. 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.

      Delete
  3. 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.

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    1. 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

      Delete
    2. "In Australian they were making humansized mice"

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

      Just one letter.

      Delete
  4. Do you have an inside story to this man who had been in a wheelchair for 10 years but still managed to get stem cell from Hammersmith Hospital?
    https://www.mssociety.org.uk/care-and-support/online-community/community-blog/everything-is-different-now---roys-hsct-story?utm_source=Email&utm_medium=link&utm_content=2018.10.23_Buzz_Oct_everyone_outside_London%20(1)November%2001,%202018&utm_campaign=2018M7202_0494&spMailingID=4420066&spUserID=MjMzMTE5MDkxODkS1&spJobID=1150078484&spReportId=MTE1MDA3ODQ4NAS2L

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  5. Any toughts on the usefulness of this therapeutic approach for MS patients with spinal cord lesions?

    ‪Three patients with spinal cord injuries are now able to walk with targeted electrical stimulation of the spinal cord‬
    https://www.nature.com/articles/d41586-018-07251-x

    https://www.cbsnews.com/news/paralyzed-patients-walk-again-with-help-of-spinal-implant/

    Thanks,
    Marc

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  6. 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?

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  7. Macrophages help in spinal cord injury
    https://m.medicalxpress.com/news/2018-11-immune-cells-key-therapies-spinal.html

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  8. 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

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  9. Portuguese researchers are everywhere

    :)

    New clues to the origin and progression of multiple sclerosis

    https://medicalxpress.com/news/2018-11-clues-multiple-sclerosis.html

    Obrigado

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  10. 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

    ReplyDelete

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