Saturday, 3 September 2011

Case report: Is MS caused by a retrovirus?

In response to an email request for more information on the following case report: 

Maruszak H, Brew BJ, Giovannoni G, Gold J. Could antiretroviral drugs be effective in multiple sclerosis? A case report. Eur J Neurol. 2011 Sep;18(9):e110-1. doi: 10.1111/j.1468-1331.2011.03430.x.

This is a case report of a man aged 26 who was diagnosed with possible MS in 1985 within several months of an initial confirmation of acute HIV-1 infection. Over subsequent years his neurological deficits and clinical investigations confirmed the diagnosis of RRMS. RRMS episodes were treated with systemic steroids with some effect. The patient could not tolerate interferon beta or glatiramer acetate therapy. The multiple system presentation of the RRMS, his young age and frequency of episodes all predicted a poor prognosis for his MS. During this period, the patient’s HIV condition remained asymptomatic and stable with a CD4 T cell count within normal limits and relatively moderate HIV viral load (<20,000 copies/ml). After 10 years from his acute HIV infection with an HIV RNA viral load of 19,000 copies/ml and a CD4 T cell count of 400 cells/ml (normal 500-1000 cells/ml) the patient was commenced on a highly active antiretroviral therapy (HAART) regimen with drugs known to have good central nervous system (CNS) penetration. In the past 14 years since he has been on HAART he has suffered no further neurological episodes. 

"Why is this case report important?"

"It is very important for several reasons. Firstly, we don't know what causes MS and several people have proposed over the years that MS is due a virus and more specifically a retrovirus. This is not a new hypothesis."

"If MS is due to a retrovirus the possible impact of HAART on the course of MS in this case cannot be ignored."

"Should we not explore this further?"

"This is another example of why case reports are so important."

CoI: Julian Gold is an honorary Professor in our unit and I'm a co-author on this paper.

Other articles of interest:

Antony JM, Deslauriers AM, Bhat RK, Ellestad KK, Power C.
Biochim Biophys Acta. 2011 Feb;1812(2):162-76. 

Perron H, Lang A.
Clin Rev Allergy Immunol. 2010 Aug;39(1):51-61.

Perron H, Bernard C, Bertrand JB, Lang AB, Popa I, Sanhadji K, Portoukalian J.
J Neurol Sci. 2009 Nov 15;286(1-2):65-72. 

Christensen T.
Rev Med Virol. 2005 May-Jun;15(3):179-211.

Clausen J.
Int MS J. 2003 Apr;10(1):22-8. 

Kolson DL, González-Scarano F.
Ann Neurol. 2001 Oct;50(4):429-30.

Rasmussen HB, Lucotte G, Clausen J.
J Neurovirol. 2000 May;6 Suppl 2:S80-4. 

Haahr S, Munch M.
J Neurovirol. 2000 May;6 Suppl 2:S76-9. 

Rudge P. 
J Neurol Neurosurg Psychiatry. 1991 Oct;54(10):853-5. 

15 comments:

  1. Prof G, what does HAART do to other viruses in the body- eg EBV?

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  2. Prof G,

    Why not start a small trial c.10 patients and try HAART (or another anit-viral)? Some of these theories have got to start being tested - if a virus is involved then an anti-viral is the only way I can think of to test the theory.

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  3. If MS is caused by a retrovirus then how can it also be caused by EBV?

    Is it possible he just went into remission?

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  4. Re: "What does HAART do to other viruses in the body- eg EBV?"

    An important question; some anti-retrovirals do have laboratory evidence that they work against herpes viruses. But in general they do not suppress EBV viral loads in the body.

    Lin et al. Anti-human immunodeficiency virus agent 3'-azido-3'-deoxythymidine inhibits replication of Epstein-Barr virus. Antimicrob Agents Chemother. 1988 Feb;32(2):265-7.

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  5. Re: "If MS is caused by a retrovirus then how can it also be caused by EBV?"

    The million dollar question. This is the so called "dual viral infection hypothesis". There is a large literature on how human endogenous retroviruses interact with herpes viruses including EBV. Watch this space!

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  6. Re: "Why not start a small trial c.10 patients and try HAART (or another anit-viral)?"

    Something we are very keen to do; we would however need funding.

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  7. Re: "What's a retrovirus?"

    A retrovirus refers to a family of RNA viruses that are able to reverse transcribe their RNA code into DNA. The DNA can then insert itself into the cells DNA and become part of the genome. If this effects germ cells (eggs in the ovary and/or sperm in the testes) these viruses can then be passed on genetically. There are large family of these viruses; HIV is one of these viruses and our genomes have literally 100's of copies of human endogenous retroviruses (HERVs). HERVs are probably an important part of our evolution; they are one of the drivers of changes in our DNA code. I will do some additional, more detailed, post on this topic.

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  8. I wonder if this has something to do with IL7R disregulation as well? Both are implicated in MS and HIV and possibly regulating the one impacts the other.

    I wonder if HAART has an impact on MS?

    Interesting...

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  9. One thing that is also interesting...

    Neopterin levels are high in people with MS.

    AZT reduces neopterin in serum:
    http://www.jstor.org/pss/30133535

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  10. Neopterin know you're taking the first time I saw Prof G in the lab was with a bucket of pee hunting for neopterin

    http://www.ncbi.nlm.nih.gov/pubmed/9055793

    Maybe he will comment on this

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  11. That was 1997. What happened after that?

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  12. Re: "Neopterin"

    We are still working on Neopterin; it is a very sensitive marker of inflammation. Why things did not move on since 1997 is that the community are reluctant to go the biomarker route. I have noted a shift in emphasis more recently. Our project to try and identify people at risk of MS will include neopterin as a biomarker.

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  13. Please pardon my ignorance but could the new DRACO'S be potentially relevant to this discussion?

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    1. Please pardon mine

      A DRACO is new broad-spectrum antiviral approach, dubbed Double-stranded RNA (dsRNA) Activated Caspase Oligomerizer (DRACO) that selectively induces apoptosis in cells containing viral dsRNA, rapidly killing infected cells without harming uninfected cells.

      Double-stranded RNA Activated Caspase Oligomerizer (I love acronyms), and it’s basically designed to detect any long double stranded RNA, so we’ve created chimeric proteins where one end will detect the chimeric RNA — the double-stranded RNA — and then the other end will trigger apoptosis, or cell suicide. So the net effect is that these DRACO molecules can go inside all the cells in your body, or at this moment, inside all the cells in a mouse, and if they don’t find anything, then they don’t do anything. But if they find a viral infection, if they find a viral double-stranded RNA, then that will activate the back ends to trigger cell suicide, and that will kill the infected cell. That terminates the infection.

      However these are experimental at the moment

      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144912/

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