Saturday, 17 March 2018

Charcot 3: does an anti-viral inhibit MS?

Does an anti-viral inhibit MS? Charcot 1 is still not published (nudge, nudge) but it didn't work but that didn't surprise me as the treatment agent prevented virus integrating into the DNA, which was targeting a virus that had already integrated.

However there was anecdote of disease remission after taking the drug. It has happened again:

Drosu NC, Edelman ER, Housman DE. Could antiretrovirals be treating EBV in MS? A case report. Mult Scler Relat Disord. 2018 Feb 27;22:19-21.

We present the case of an HIV-negative patient clinically diagnosed with relapsing-remitting MS who achieved significant disease improvement on Combivir (zidovudine/lamivudine). Within months of treatment, the patient reported complete resolution of previously unremitting fatigue and paresthesiae, with simultaneous improvements in lesion burden detected by MRI. All improvements have been sustained for more than three years. This response may be related to the action of zidovudine as a known inhibitor of EBV lytic DNA replication, suggesting future directions for clinical investigation.


Zidovudine (ZDV), also known as azidothymidine (AZT) It works by inhibiting the enzyme reverse transcriptase that HIV uses to make DNA and therefore decreases replication of the virus. Lamivudine is a nucleoside reverse transcriptase inhibitor and works by blocking the HIV reverse transcriptase and hepatitis B virus polymerase.



The person took the drug and got better, is this due to drug or because of "regression to the mean" and they got better because they were going to get better anyway? There is one way to find out and that is to try it again. I hope they have stumbled on to a winner.

10 comments:

  1. Could you explain the difference between the possible AZT anti-EBV mechanism and the difference to RTX and EBV and Famvir? Thanks.

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  2. Please Dr Mouse, I too think this is a potential game changer but can you explain the exact difference between the modes of action between Combivir used in the Drosu et al research and Raltegravir ( used in the Inspire study - Charcot 1). As I understand things- and I am a non-scientist – Raltegravir stops viruses like HIV from entering the cell. It is what is called an “integrase inhibitor” stopping insertion (integration) of viral DNA into the DNA of the host. What might be argued is that Raltegravir didn’t work because if MS is caused by an endogenous retrovirus the “infected” DNA or RNA is already in the cell, it’s part of your DNA. If you accept the endogenous retrovirus theory would you say that Combivir worked because it stopped the endogenous retrovirus-W family (HERV-W) from replicating inside the cell. Combivir is I believe a nucleoside reverse transcriptase inhibitors (NRTIs) which stops a virus like HIV already inside the cell from making copies of itself. Interestingly in Prof Gold’s original 2011 case report the HIV positive patient whose MS symptoms disappeared was taking Lamivudine (which is combined with zidovidine in Combivir) from 1996 – 2010 – longer than any of the other HIV drugs he was taking . Doesn’t this suggest that we should be looking at a nucleoside reverse transcriptase inhibitors (NRTIs) like Combivir ? And given that this drug is now a generic should we be looking at crowdfunding or should us MSers just go online and buy it?

    ReplyDelete
    Replies
    1. The combination of lamivudine and zidovudine is composed of two nucleotide reverse transcriptase inhibitors, so it stops an RNA virus (like HIV) converting itself to DNA which it does before replication. However EBV is a Herpes virus, which is a DNA virus. So as there is limited obvious reason why raltegravir works, because it stops virus integrating into the DNA. EBV is episomal so is not integrated. HERV is already integrated

      HAART has entry inhibitors and protease inhibitors

      Famcyclovir is a herpes directed drug that activated form inhibits viral DNA polymerase, thus impairing the ability of the virus to replicate within the cell.

      Delete
  3. Please Dr Mouse, I too think this is a potential game changer but can you explain the exact difference between the modes of action between Combivir used in the Drosu et al research and Raltegravir ( used in the Inspire study - Charcot 1). As I understand things- and I am a non-scientist – Raltegravir stops viruses like HIV from entering the cell. It is what is called an “integrase inhibitor” stopping insertion (integration) of viral DNA into the DNA of the host. What might be argued is that Raltegravir didn’t work because if MS is caused by an endogenous retrovirus the “infected” DNA or RNA is already in the cell, it’s part of your DNA. If you accept the endogenous retrovirus theory would you say that Combivir worked because it stopped the endogenous retrovirus-W family (HERV-W) from replicating inside the cell. Combivir is I believe a nucleoside reverse transcriptase inhibitors (NRTIs) which stops a virus like HIV already inside the cell from making copies of itself. Interestingly in Prof Gold’s original 2011 case report the HIV positive patient whose MS symptoms disappeared was taking Lamivudine (which is combined with zidovidine in Combivir) from 1996 – 2010 – longer than any of the other HIV drugs he was taking . Doesn’t this suggest that we should be looking at a nucleoside reverse transcriptase inhibitors (NRTIs) like Combivir ? And given that this drug is now a generic should we be looking at crowdfunding or should us MSers just go online and buy it?

    ReplyDelete
  4. Look what i found :)

    https://www.youtube.com/watch?v=0d6v-2Xc-5E

    Would like to see Prof G talk more about anti retroviral failure in stoping ms
    http://multiple-sclerosis-research.blogspot.com/2016/10/researchspeak-inspire-trial-results.html

    You did the study i fails what had you learn after all?

    Are you still believing Ebv is diving the disease ?

    What when wrong in your study?

    Obrigado

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    Replies
    1. Would love to know too...

      Delete
  5. The problem with Combivir is that it can cause lipoatrophy-lipodystrophy :/

    ReplyDelete
  6. Multiple sclerosis patient walks after taking HIV drugs (from 2015)

    http://www.bbc.com/news/uk-england-sussex-34659771

    ReplyDelete

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