Kate Benson

Dr. Ian Lipkin and Dr. Mady Hornig, Use Deep Sequencing and Proteomics to Hunt CFS Viruses

Dr. Ian Lipkin, Hunting Down Viruses using Deep Sequencing, as Seen in the NYTimes.

In the end, cutting edge technology may be the game-changer in chronic fatigue syndrome – a condition that strikes an estimated 1-4 million patients in the United States.

Viral involvement and immune system abnormalities have long been suspected as contributing or causing the disease. But for many reasons, including the multiple definitions used, delays in diagnosis and small sample size, study results have been mixed.

Now however, researchers have powerful state-of-the art tools at their disposal, and the Center for Infection and Immunity at Columbia University stands at the nexus.

“We have the best tools to do the work and the funding required to pursue it,” said center director Dr. Ian Lipkin, “and will bring the very best possible minds to the problem irrespective of institution. We will be taking a broad, open-minded approach to the problem.”

The CII, and other institutions, using venture philanthropist seed money provided by the Glenn Hutchins Foundation, will focus their efforts on three components:

  • Identification of disease markers.
  • Disease mechanisms.
  • Finding the specific bacteria, fungi and or viruses – alone or in combination – responsible for causing or exacerbating the disease.

The research will be two-pronged and coordinated by Dr. Mady Hornig, an associate professor of epidemiology at the Mailman School of Public Health and director of Translational Research at the CII.

Multiple deep sequencing platforms will be used for pathogen discovery.

“One of the challenges in a chronic disorder like ME/CFS is that we may be dealing with a situation where the trigger, which we have good reason to believe is an infectious trigger, may precede the onset of symptoms or recognition of the chronicity of the pattern by quite a long period,” said Dr. Hornig. “The agent could have a hit and run; its levels reduce over time, or induce a biologic situation even in the absence of continued high levels of infectious agent.”

Unlike microarray chips that have a finite number of known pathogens for testing, deep sequencing allows researchers to find not only an unlimited number of varying strains of known pathogens, but novel pathogens as well.  Testing will most likely be done at a sequencing center pooling the resources of several large centers as the equipment is very expensive and personnel have to be specially trained, according to Dr. Hornig.

Researchers will be looking for patterns that are consistent across geographic areas, time and clinical status, said Dr. Lipkin.

“We show quite clearly a wide range of infectious agents can trigger similar pathways in immune system that result in similar outcomes so it may well be that there are many pathogens who have capacity to cause chronic fatigue syndrome by either inducing autoimmunity or some sort of impact on the immune function which results in activation,” said Lipkin, who plans to examine other hypotheses as well depending on the results of initial tests.

Defining biomarkers through the use of proteomics will also be carried out at the Yale Keck Biotechnology Resource Laboratory as well as at Columbia University.

In terms of disease in general, biomarkers, that is proteins that carry out body functions, have been analyzed for diagnostic purposes for more than a century. Recent advances in protein analysis have expanded the opportunities. Proteomics, which is the study of proteins in a specific time frame, is currently the best bet for creating new approaches to diagnosing and treating human disease, and designing new drugs to treat disease.

“The effort in ME/CFS is to try to find some biomarkers that will be likely to identify a set of pathways that are likely to involved. That will be an enormous gain for the field and of course the patient,” said Dr. Hornig.  Biomarkers in ME/CFS can be used to create diagnostic laboratory tests as well as to determine therapy response and prognosis.

The key to maximizing the outcomes of these tests is the criteria of the patients selected, according to Dr. Lipkin. He said this will give the greatest possibility of finding objective measures for monitoring and measuring the disease. University of Miami researcher and physician Dr. Nancy Klimas, who has been involved in several clinical definitions of ME/CFS, is in charge of the cohort recruitment to draw 200 patients from five sites located throughout the U.S.

“What we want to do is start with patients who have been characterized extensively using standardized criteria established by a group of widely respected clinical researchers,” said Dr. Lipkin.

Both Dr. Lipkin, who is a board certified neurologist, and Dr. Hornig, who is a board certified psychiatrist, stress that while they believe ME/CFS is a neuropsychiatric disorder because of the problems with concentration, memory and autonomic nervous system involvement, they do not consider it psychosomatic.

“It’s very difficult in my mind to make this a psychological disorder,” said Dr. Hornig,“We do patients a disservice if we focus solely on secondary phenomena of being disabled or being unable to carry on life to your capacity – that shouldn’t ever be viewed as being the primary problem.”

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  • Chris

    Nice writeup Kate. Thanks for the continued coverage. When you spoke with Drs. Lipkin and Hornig, did they provide a general timetable for the study?

  • Pingback: Interessant artikkel om Dr. Ian Lipkin og Dr. Madys forskning og meninger om ME | ME-nyheter

  • Shirley

    Kate, did you get that line that both Dr. Lipkin and Dr. Hornig believe that ME “is a neuropsychiatric disorder” from them or was that your own words? Most experts call ME a neuroimmune disorder, so this was confusing. “Neuropsychiatric disorder” would imply that there is a primary psychiatric disorder with a neurological cause, and not a psychiatric disorder that is simply secondary to having the neuroimmune illness. If a main researcher is calling this illness neuropsychiatric, then I would be very suspect of the entire project. Could you clarify?

    Thank you however for the rest of the article and for helping spread awareness on ME!

  • Nita

    Why isn’t an infectious disease specialist in charge of the research?

  • Justin Reilly, esq.

    Thank you for this excellent article! (i do have an issue with Dr. Hornig’s characterization of ME as a neuropsychiatric disorder. The symtoms she lists- problems with memory, cognition and ANS are neurological symptoms, not psychiatric)

  • Pingback: ‘Dr Ian Lipkin and Dr Mady Hornig use deep sequencing and proteomics to hunt CFS viruses’, Cure talk website, 4 November 2011 | ME Association

  • Kate Benson

    @ Nita – One reason Dr. Lipkin is doing this project is he is considered the best in the world when it comes to tracking and identifying viruses. You can learn more about him in the New York Times article, “A Man From Whom Viruses Can’t Hide,” written in 2010 by science writer Carl Zimmer. He was actually asked by the CDC to look into Borna viruses in CFS in the 1990s and although he did not find an association he said he recognied then that patients were very sick. New tools may yield better answers.

    @ Shirley – I always uses my sources wording whenever possible. Both Dr. Lipkin and Dr. Hornig refer to ME/CFS as neuropsychiatric and those terms were the ones listed by Dr. Lipkin. Neuropsychiatric is a very broad term – Lyme disease, Alzheimer’s dsease, MS and Parkinson’s disease can also have neuropsychiatric aspects as well for example, but it doesn’t make them a psychological or psychosomatic disorder.

    Although having a psychological disorder has never made anyone immune to organic disease.

    Depression for example is a very natural response to having a severe disease, particularly where there is some stigma, and may be co-morbid with many diseases. Or for example, a classic response of animals when sick is they sleep more and there is less movement – according to Dr. Hornig, a very classic reaction to an infectious agent – but one that also mimics depression.

    ME/CFS is a very complex disease or group of diseases and it will take time to tease apart all the variables. There is much that is unknown in science and medicine.

  • Oni

    Hello Kate
    Thanks for the article. Just a clarification: ”… while they believe ME/CFS is a neuropsychiatric disorder because of the problems with concentration, memory and autonomic nervous system involvement, they do not consider it psychosomatic.”

    Was ‘neuropsychiatric disorder’ a term used by Dr Lipkin and Dr Hornig during the interview or was it a term you chose to use in the writing of this article?

    I believe the term is incorrect and confusing. Neurological disorder is the correct term to describe ME/CFS.
    It is also an auto-immune illness and much more as scientists in the field have known for many decades.

  • Zac

    Thank you for all your informational articles

  • Eric

    If treating patients with a drug that depletes B-cells (Rituximab) leads to substantial improvement in around 2/3 of cases and even cures some, i would not call that disease neuropsychiatric. Even though ME/CFS produces neuropsychiatric impairments.

    But i’m not a doctor and am happy Ian Lipkin is getting involved in this disease. Also the RItuximab findings need to be replicated in larger studies, of course.

    Besides that, thanks for the article.

  • Pingback: Viral studies to continue in chronic fatigue syndrome; two viruses ruled out | Cure Talk