Tuesday, 6 November 2018

When Mist Becomes Most

Prof Burt from Chicago has presented "At the Limits 2018"
and shown the headline results of the MIST trial (A randomised, assessor blinded clinical trial), which finished recruitment in 2016. 

Very Interesting, but you'll have to wait until the results are announced/published before we will . Sorry but it is only fair to the USA, British,Swedish and Brazilian Teams to keep quiet.

However, before he started talking about the results, in his own words “Don’t do Progressive disease”

People with active disease respond best to this treatment which is cyclophosphamide and anti-thymocyte globulin followed by stem cells to block the infection risk of loss of neutrophils.

Next up is the Trial. Maximizing Outcome of Stem Cell Transplantation (MOST), We look forward to seeing what is planned.

9 comments:

  1. When is this farce of treatment of progressive MS with neuroinflammatory treatments going to end?

    Cyclophosphamide, arguably the most potent immunosuppressive DMD used in most HSCT protocols, failed to halt progression in MS as Dr. Burt and Dr. Freedman have stated publicly multiple times in the past.

    What chance then does ocrezulimab, cladribine or siponimod stand in progressive MS other than in selection bias or statistically manipulated trials?

    You will get worse on these DMDs just slightly slower (< 25% above placebo) but to the very same debilitated endpoint in your disease process. This even takes into account length dependent axonopathy hypothesis and time delay hypothesis, which are obliterated as one ages and lose their reserve capacity.

    Please MD and MD2 start commenting on ways to inhibit hot microglia or A1 astrocytes and how to stop neurodegeneration and stimulate remyelination and neurorestoration. Clearly neuroinflammation, by B or T cells, makes up a minuscule part of the answer in progressive MS.

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    Replies
    1. We comment on whats published and near to the clinic,
      If you want the repair and restore do you want us to comment on animal studies?

      Delete
    2. I am probably in the minority but yes. I appreciate MD2 and MD's real thoughts on treatment of progressive MS.

      There is no possible way that current "neuroinflammatory only model" is the answer in progressive MS treatment. It is like we are trying to ram a square peg constantly into a round hole and it will never work.

      When HSCT, the most potent inflammatory DMD of all, fails to treat progressive MS then is it not time to change strategies?

      Delete
    3. Problem has been the either/or approach and these camps fighting each other over too many years, perhaps because of limited resources since funding is tight, perhaps other reasons, but MD, MD2, Prof G and indeed most of those writing on this Blog have come out on various occasions to search for evidence that combining approaches might be best. Industry as well as non-profit are coming around to this concept, and the discussion will be much rather what to combine with what. Finally, if you say HSCT "doesn't" work be mindful not to step in the same trap as most of us did at some point taking response on EDSS as outcome since it is not valuable in people with progressive MS, particularly at a more advanced stage.

      Delete
  2. "No inflammation no response"

    https://www.youtube.com/watch?v=oTWTe3nZ4hE&t=18s

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  3. There are papers from 2011 - 2013 discussing the use of chondroitinase abc in combination with anti nogo a antibodies for spibal cord treatment...in rats.

    https://www.ncbi.nlm.nih.gov/m/pubmed/23790207/?i=2&from=/23839053/related

    So what are the biggest barriers to phase I studies in people? The initial cost (million plus) for the trial? The route of administration if it needs to be spinal? No idea of the pharmokinetics?

    Would be nice to see what Christopher Reeve foundation is funding.

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    Replies
    1. Anyone can go to their website to see what they fund...

      Delete
    2. I didn't realize that his wife died from cancer :(

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    3. Yes..lung cancer at 44..Tragic for their son.

      "Rather, they are passive smokers. This means that they breathe in the cigarette smoke that is exhaled by others.

      For example, consider the very tragic death from lung cancer of Dana Reeve, who long devoted herself to the care of her paralyzed husband, the actor Christopher Reeve. Ms. Reeve had never smoked actively, but she did work as an entertainer, singing in smoke-filled bars and restaurants. That was probably the genesis of her cancer.

      Sometimes passive smoking is as simple as the unfortunate child who is exposed for years to the smoke of his cigarette-addicted parents. Some years ago, when legislation was passed in Scotland limiting cigarette smoking in public places, for example, the incidence of a whole range of smoking related problems like asthma, chronic bronchitis and pneumonia dropped dramatically among children there within a year.

      In addition, some people who smoke a pipe or cigars say they don’t smoke. Nobody has ever shown that smoking pipes or cigars is actually safe.

      In fact, many physicians and researchers believe that passive smoke — the smoke exhaled by others — is potentially even more dangerous than actively inhaled smoke.
      The reasoning is this: When someone smokes actively, the hot acrid fumes taken in are such an irritant that they often trigger an instant cough, thus limiting exposure to lung tissue, at least to some extent. Passive smoke, on the other hand, is dilute and not so hot. As a result, it tends to be inhaled and drawn in more deeply without causing an immediate reaction.

      What is quite clear is that lungs exposed to cigarette smoke — whether it is actively or passively inhaled — are black and pigmented from all the chemicals in the smoke, many of which are cancer-causing.
      There’s also the issue of “third-hand smoke,” in which particles and chemicals exhaled can settle on surfaces like chairs and desks and pose a further health hazard."

      Another piece of the puzzle is that cigarette smoke is not the only known cause of lung cancer.

      It is well documented that in some parts of the country, people are exposed to radon gas, a radioactive substance that leaks from the ground and that has the potential to cause lung cancer.

      https://consults.blogs.nytimes.com/2009/06/22/never-smoked-but-at-risk-for-lung-cancer/

      Delete

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