Friday, May 25, 2012

WPI back on track?

The WPI has published its new research program. From its website (highlights are mine):
[Whittemore Peterson Institute] Current Research Program
Friday March 25th 2012

1. Pathophysiology of chronic fatigue syndrome

This National Institutes of Health (NIH) funded study proposes to identify pathogens associated with chronic fatigue syndrome (CFS). Initially, this study relied upon microarray technology to detect viruses potentially associated with CFS. However, now, under the direction of Dr. Vincent Lombardi, this study will instead utilize unbiased next generation sequencing technology. This state-of-the-art method is not subject to the limitations of viral microarrays. Not only does this technology have the capacity to identify any viruses, it also has the ability to identify any pathogens, associated with CFS. Additionally, it will allow us to perform transcriptome analysis, which has the ability to identify differences in the immune system when compared to those who do not suffer from CFS. Therefore, all of the original specific aims of the grant will be addressed; however, transcriptome analysis may provide additional knowledge that could not be obtained using originally proposed methods. This study also proposes to investigate dysregulation in the interferon response associated with CFS.

[From the PDF]
New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome

The original Aims of the National Institutes of Health (NIH) RO1 grant were to identify both novel viral infections and genetic susceptibility factors in European and American cohorts of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) patients. The principal investigator (PI), Dr. Vincent Lombardi, will pursue these Aims using more advance technology in order to discover pathogens (known or unknown infectious agents) and their associated immune responses in ME/CFS.

The overall goal of this research project is to define viral and host parameters that correlate with distinct disease phenotypes in European and American cohorts of ME/CFS patients with diagnoses fulfilling the Center for Disease Control (CDC) definition and Canadian Consensus Criteria for ME/CFS. To do this, we will obtain blood samples from ME/CFS patients and healthy control subjects from specific medical practices, with the recent approval from the University of Nevada, Reno Biomedical Institutional Review Board (IRB). We will utilize next generation sequencing by synthesis (SBS) technology to detect novel virus mRNA and evaluate transcriptome differences between ME/CFS subjects and healthy control subjects. Any pathogen infection will be confirmed with a combination of quantitative PCR (QPCR) and culture methods. Additionally, we will evaluate serum chemokine and cytokine profiles using multiplex suspension antibody arrays on a Luminex platform. Finally, we will evaluate HLA and KIR genotypes and investigate possible defects in the type I interferon signaling pathway.

At the conclusion of this study, we anticipate identifying any pathogens uniquely associated with ME/CFS. We also anticipate identifying differences in the lymphocyte transcriptome as well as any differences in HLA, KIR and interferon immune parameters.
Some observations from this:
  • They are still looking for "knowns and unknown" "pathogens uniquely associated with ME/CFS".
  • They are switching from an microarray-assay to next generation sequencing (next generation "sequencing by synthesis – SBS").
  • They are doing a transcriptome analysis
  • They are still focusing for cytokine differences
Sure sounds partially promising.

The question is: Will this yield once again results that are not based in reality, unreproducible by anybody else? After all, Dr. Lombardi worked together with Dr. Mikovits on her seminal work, and he is quite firmly rooted in Woo-Land. We'll see.

2. Pathogen and biomarker discovery in Gulf War illness

This Department of Defense (DOD) sponsored project will utilize next generation sequencing technology in order to identify differentially transcribed genes associated with Gulf War illness (GWI). This information will be used to better understand the pathophysiology of GWI. Additionally, this information will be used to identify potential biomarkers for diagnostic purposes and evaluation of treatment progress.

From the PDF:
Pathogen and Biomarker Discovery in Gulf War Illness

The goal of this study is to identify potential biomarkers, including pathogens, associated with Gulf War illness (GWI), which in turn will afford physicians the necessary tools to make more accurate diagnoses. This study will be conducted under the direction of Dr. Vincent Lombardi as the principal investigator (PI).

GWI is a chronic multi-­‐symptom disorder affecting approximately one third of the veterans and civilians who served during the Persian Gulf War (Desert Storm 1990-­‐ 1991). It is a syndrome primarily described by a spectrum of symptoms, innate immune abnormalities and opportunistic infections. A wide range of acute and chronic physical symptoms are associated with GWI including fatigue, musculoskeletal pain, gastrointestinal dysfunction and cognitive problems. Unfortunately, diagnosis of GWI is difficult in that no discrete biomarkers or etiological agents have been identified. A greater understanding of the innate immune system and the associated opportunistic pathogens may provide insight into the pathophysiology of this disease.

In order to explore this issue, we will recruit subjects diagnosed with GWI who served during the Persian Gulf War, whether or not actually deployed to Iraq and surrounding areas, along with healthy control subjects, following approval of the University of Nevada, Reno Institutional Review Board (IRB). We will conduct lymphocyte transcriptome analysis of GWI subjects and compare the results to the same analysis of healthy control subjects. The transcriptome is reflective of the genes that are being actively expressed at any given time; therefore, the lymphocyte transcriptome represents a window into the innate immune system, potentially leading to an understanding of GWI pathogenesis. Transcriptome analysis also has the ability to identify any pathogens present in the immune cells, potentially identifying an etiological trigger.

We look forward to commencing this important study after obtaining IRB approval of the study protocol.

3. Cytokine dysregulation in chronic fatigue syndrome

Cytokine and chemokine dysregulation is one of the most consistently reported observations in individuals with ME/CFS; nevertheless, the mechanism of this dysregulation remains unknown. The acute onset and epidemiological patterns of ME/CFS etiopathology support the involvement of a pathogenic trigger. Consistent with this observation, is the fact that the innate immune system responds to infection by producing proinflammatory cytokines and chemokines. The microbial pattern recognition receptors, Toll-like receptors (TLRs) 3 and 4, are activated by pathogen-derived dsRNA and LPS, respectively, to produce these proinflammatory cytokines. This system is tightly regulated; however, in patients with ME/CFS, it is constitutively active. The focus of this research project is to better understand the mechanism of this dysregulation.

4. Biomarker discovery in neuro-immune and inflammatory diseases

Previously, we identified a cytokine/chemokine signature with high specificity and sensitivity in diagnosing ME/CFS patients. Our project will extend this signature to other inflammatory and neuro-immune diseases, providing physicians with necessary tools to delineate closely related neuro-immune and inflammatory diseases.

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