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

Kate Benson, trialx.com, Nov 04, 2011: 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 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 requirement 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, who is also board certified as a psychiatrist. “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.”