Friday, 22 January 2016

CrowdSpeak: so near yet so far out of reach

We are almost there with your first Crowding Funding initiative; Thank you. #CrowdSpeak #MSBlog #MSResearch

"Your Crowdfunding initiative is close to 90% of its target; I am truly amazed at how quickly we have done this and your enthusiasm for the project. Thank you."




Click here to find out more!

"The first study done under the Charcot Project umbrella, the INSPIRE or raltegravir trial, finished last year and was negative. We will be submitting two papers on the results in the next few weeks and presenting the results at a congress sometime this year. "

"To take the Charcot project forward we have decided to focus on EBV component of the viral jigsaw puzzle in the next trial. To make the case regarding the retroviral component of the study we need more biomarker data whether or not the anti-retrovirals are having an effect on HERVs (human endogenous retroviruses) and we also need more epidemiology data on whether or not our observation of lower MS rates in HIV infected individuals is due to anti-retrovirals or some other factors."

"You may recall that you the community suggested crowdfunding and had a vote between two projects (Charcot project 2 vs. the ZEUS Trial). You chose the former and gave the trial its name (ARTEMIS - Antiretroviral Treatment for Epstein-Barr Virus in MultIple Sclerosis) and you helped resolve some early design questions. For example, the following is your feedback on some of the inclusion and exclusion criteria."


"We love the name ARTEMIS as it is the name of a Greek moon goddess often portrayed as a virgin huntress. The primary aim of the Charcot Project is to hunt down the viral cause of MS; so having a trial named after a huntress seems appropriate. Even if we simply focus on the EBV component of this study the namer ARTEMIS still works; (ARTEMIS - AntiviRal Treatment of Epstein-Barr Virus in MultIple Sclerosis) "

"Some may ask what is the rationale for doing this study? There is emerging evidence that EBV and HERVs are involved in MS. Some of us in the MS community are of the opinion that EBV causes MS and that if you can prevent people becoming infected with EBV you may prevent MS. We don't know how EBV causes MS. One of the theories that we are investigating is that EBV causes MS via its interaction with HERVs."

"HERVs are viruses that live in our genome; about 6-8% of the human genome is HERVs. Why do we have so many HERVs in our genome? Evolution has selected for them because they must give us, and other mammals, a survival advantage. For example, one HERV protein is critical for the development of the human placenta. Mammals who don't have a placenta (marsupials) don't have this HERV. As HERVs are sort of 'foreign', the human body has developed intricate ways of detecting them and if they are found to be expressed in a cell the cell's internal immune system flags that it is infected with a virus so that the immune system can eliminate the cell. This so called danger signal is often is what is needed to activate the external immune system and if this happens to be an autoreactive immune cell it can trigger autoimmunity. Interestingly, there is a very rare disorder due to mutations in the systems that detect and suppress HERVs in cells. The children with these mutations present with multiple autoimmune diseases indicating that uncontrolled HERV expression can drive autoimmune disease. You may be aware by now that there is emerging data that MSers have evidence of increased HERV expression in the cells of the peripheral blood and possibly in their brains as well. At present we don't know if MS causes HERV expression or does HERV expression cause, or drive, MS? This is one of the reasons we are so interested in HERVs."

"So how do EBV and HERVs relate to each other? It turns out that herpes viruses, in particular EBV, are potent transactivators of HERVs. In other words EBV does something to wake-up the sleeping HERVs in our genome and increases their expression. This is the rationale for using drugs to reduce EBV activity in the hope they will suppress HERVs."

"I am aware that what I am saying above is complex, but I hope it sets out the rationale and makes the case for using an anti-EBV drug in MS. The proposed ARTEMIS study will hopefully provide us with necessary virological and safety data to make the case for doing a larger efficacy study in MS."




"This remains a community project so please feel free to comment. Thank you."

CoI: multiple and Team G will be recipients of a grant from Crowdacure to perform this research

11 comments:

  1. prof do you have a collection box at the blizard? have some coppers i want to donate to get you to the target

    ReplyDelete
    Replies
    1. Yes, we do you are welcome to pop-in and donate. Or we can come to you?

      Delete
  2. Great scientific endeavour! 100% behind you for the viral hypothesis. By whom EBV is replicated? How does it spread within the body?

    ReplyDelete
  3. Totally got everything in this post, Prof G. Very well explained.

    Big Pharma ought to make up the deficit. Get them donate too. You do a lot for them and their steering committees. They can afford it.

    ReplyDelete
  4. ~900 pounds, almost there! Will you see how the f drug interacts with "classic" DMTs? An antiviral treatment might be a good candidate in a "cocktail" therapy.

    ReplyDelete
  5. How can you sign up to express interest in taking part in the trial?

    ReplyDelete
  6. "...one HERV protein is critical for the development of the human placenta. Mammals who don't have a placenta (marsupials) don't have this HERV." Wow - that I did not know - fascinating. Takes me back to my wide-eyed wonderment during evolutionary biology lectures at uni! I'm really excited by this research.

    ReplyDelete
  7. Profs, I admire your work and am sure you will meet the required cash target. I have not contributed as I felt let down by Charcot 1. We know it failed, but there has been no real transparency or information. How do I know that I wouldn't be throwing good money after bad? Was the hypothesis for Charcot 1 wrong, or the trial design or the drug selected. Was there any information from Charcot. 1 which can be used to reduce the risk of another failure for Charcot 2?

    ReplyDelete
    Replies
    1. I hope you can understand that the results stay under wraps until they are presented and published. That is the scientific way. In Charcot 1 a hypothesis was tested and it failed, I can't speak to the trial design but the drug had anecdote as its basis and the logic over say HAART is difficult, Charcot 2 will not start if the powering isnt done so this is what the Crowdacure is about. I suspect the answer of this can go on the blog as the answer is simply going to be a number. i.e. how big a trial needs to be.

      Delete
  8. What I find most interesting of all the effort to Charcot 2 is not nor Famciclovir able to inhibit EBV, but his relationship with MS, as the virus can trigger MS, which the pattern of viral load for it, and it relates to genetic factors such as HLA DRB1 * 15 and own HERVs. I downloaded and read all the publications of "HERVs & Diseases - First International Workshop
    Human Endogenous on
    Retroviruses and Diseases", even there they addressed the hypothesis "EBV infection - HERVs - MS", can actually be a connection ...
    EBV appears to be a very heterogeneous and opportunistic virus ...
    Making a pretty crazy parallel here in Brazil the FioCruz (Oswaldo Cruz Foundation) and other Scientific Research Institutions are "knocking heads" to try to understand microcephaly epidemic causality with the infection Zika Virus.
    It is already known that the virus disrupts the placenta and actually reaches the fetus, but why not all mothers of babies infected by ZV develops microcephaly, why the infection is asymptomatic in many ZV, as ZV may be causing cases of Guillain Barre Syndrome? It does seem to be a relationship between virus infection, maybe other previous viral infections, viral load patterns, environmental factors and genetic who knows (what I did not bet much for the Brazilian population is well amalgamated). They are virus very "cunning" ...

    ReplyDelete

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