Deep Sequencing & Proteomics to Hunt CFS Viruses

[Guest guest]

I’m far behind in posting, because of 1) bad health and 2)

a lot of members read *Help ME Circle* at their office and

I didn’t want to overwhelm them with messages during the

holidays. I will keep the date of editing.

~jvr

````

http://j.mp/vMAcYa

Cure talk

Dr. Ian Lipkin and Dr. Mady Hornig, Use

Deep Sequencing and Proteomics to

Hunt CFS Viruses

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 (http://bit.ly/AozFbv) 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.

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.*