Monday, 11 April 2016

Anti-viral for MS, the alternative charcot project

Curtin F, Vidal V, Bernard C, Kromminga A, Lang AB, Porchet H.
Serum pharmacokinetics and cerebrospinal fluid concentration analysis of the new IgG4 monoclonal antibody GNbAC1 to treat multiple sclerosis: a Phase 1 study.MAbs. 2016 [Epub ahead of print]

GNbAC1 is a humanized IgG4 monoclonal antibody antagonist of Mulitple Sclerosis Retrovirus Envelope (MSRV-Env), a protein that could play a critical role in multiple sclerosis. This randomized placebo-c,ontrolled dose-escalation study evaluated the safety and pharmacokinetics of GNbAC1 in 21 healthy volunteers after single intravenous infusion at doses of 6, 18 and 36 mg/kg. Lumbar punctures were performed at days 2, 15 or 29 to measure GNbAC1 concentrations in cerebrospinal fluid (CSF). GNbAC1 was well tolerated. Serum data show a dose-linear pharmacokinetics. A mean CSF/serum ratio of 0.12% was observed at Day 2, increasing to 0.39% at Day 15 and 0.42% at Day 29. Linear regression analysis shows a relationship between GNbAC1 CSF/serum ratio and albumin CSF/serum ratio and a relationship at the limit of statistical significance with the timing of CSF sampling.

Charcot1 might have failed but the idea is not dead. This study looks at an antibody to human endogenous retrovirus and this study looks at safety and phamacokinetic and says that if the target is in the brain 99.5%  of that injected is wasted. This also the case with anti-LINGO so if you want to target things in the brain are antibody infusions the way to go. In the long run probably not but if the antibody approach works and is safe maybe you could make a vaccine. Alternatively make a small molecule that targets the virus and gets in the brain

17 comments:

  1. Well, very interesting, even really look and get to the genetic correlation - vitamin D - Infections, can give many answers the many remaining questions about MS.

    MD yesterday were reported in several newspapers in Brazil and other countries that a Brazilian case study will be presented at AAN 68 demonstrating that Zika virus can cause in adults beyond Guillain Barré syndrome to ADEM (Acute Disseminated Encephalomyelitis).

    ReplyDelete
    Replies
    1. Vitamin D deficiency leads to excessive B-cell responses in multiple sclerosis, Ian Fyfe, Nature Reviews Neurology (2016) doi:10.1038/nrneurol.2016.49 shows an effect of vitamin d on B cells. Any comments would be useful.

      Delete
    2. The original article this refers to is here. Will have a read.
      http://www.sciencedirect.com/science/article/pii/S0165572816300455

      Delete
    3. The zika case is getting more interesting as it seems to infect the CNS - seen the Guardian article today.

      It's indeed ADEM and the symptoms are similar to MS.

      Delete
    4. Interesting but one of the big problems is Guillain Barre Syndrome, this is a demyelinating condition of the peripheral nervous system, which likewise occurs in a small fraction of people infected.

      Delete
    5. When I had a major relapse my hands went black on the palms. This was really noticeable when washing my hands or a shower, in warm or cold water it shows. My neuro said it was an autonomic nervous system problem. It has about 80% recovered and has taken two years to do so.
      This part of the peripheral nervous system?

      Delete
    6. Zika May Be Linked to Autoimmune Brain Disorder
      Researchers in Brazil detect symptoms similar to multiple sclerosis http://www.webmd.com/news/20160410/zika-may-be-linked-to-autoimmune-brain-disorder-study-says?src=RSS_PUBLIC

      Delete
    7. CNS problems impact on the periphery

      Delete
  2. The science direct article is pretty good. This is the first time I have read a clear explanation of how vit d might relate to ms, specifically b cells.

    Virus infects b cells, low vit d activates the infected b cells. Also could explain why anti cd20 therapies are so effective.

    ReplyDelete
    Replies
    1. Could be. Definitely worth following up.

      Delete
    2. Can ProfG share his thoughts at some point?

      Delete
    3. If he responds...clearly yes..although he will soon be tied up with AAN.
      I'm not getting responds to my emails so don't feel left out:-)

      Delete
  3. Why not treat relapses with an anti-viral like famvir? Before curing MS, dealing with relapses seems like the low hanging fruit as anything (sugar pills) is better than steroids.

    ReplyDelete
    Replies
    1. If someone would support the study then they would happily do it, I guess it would have to be on top of standard treatment

      Delete
  4. I'm confused. What is happening with the crowdfunded Charcot project now? Anything? I thought this was testing a method for antiviral effectivity?

    ReplyDelete
  5. Crowfunded project was not funding a grial.

    ReplyDelete

Please note that all comments are moderated and any personal or marketing-related submissions will not be shown.