Dr. Judy Mikovits (principle investigator) and the Whittemore-Peterson Institute, with collaborator Dr. Jonathan Kerr, have been awarded a 5-year, $1.6 million grant from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to support ongoing research into the disease mechanisms of chronic fatigue syndrome. Dr. Kerr is associated with St. George's College in London.
The award was announced Sep 24 on the WPI website, before news of the CFS-associated XMRV retrovirus was published Oct 8 by the journal Science. A description of the project (# 1R01AI078234-01A2) is now included in the NIH’s Research Portfolio Online.
Key Details from the NIH's Project Description
• Title: "New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome."
• Objective: “To provide significant insight into the disease mechanisms of Chronic Fatigue Syndrome so accurate testing and specific treatments can be developed with a goal of curing the disease and preventing life-threatening complications.”
• Timing: start date Sep 28, 2009; projected end date, Aug 31, 2014.
• Funding: First fiscal year funding $335,600; total funding $1.6 million.
• Project Description provided by applicant: (excerpt formatted for greater legibility, as follows).
“Chronic Fatigue Syndrome (CFS) is a complex disease estimated to affect between 0.5%-2% of the population in the Western world.
Its pathogenesis is thought to involve both inherited and environmental (including viral) components, as with other chronic inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, and atherosclerosis.
Consistent with this chronic inflammatory context, CFS patients are known to have a shortened life-span and are at risk for developing lymphoma. We hypothesize that chronic inflammatory stimulation from active and recurrent infections of multiple viruses on a susceptible host genetic background leads to the pathogenesis characterized by CFS.
The overall goal of this research project is to define these viral and host parameters in European and American cohorts of CFS patients that correlate with distinct disease phenotypes, including the development of mantle cell lymphoma (MCL) in a subgroup of the American cohort.
In Aim 1) we will identify and confirm novel viral infections in European and American CFS patient cohorts.
1.1) We will use two complementary methods for detection of novel virus mRNA: massive parallel signature sequencing (MPSS) and a custom DNA microarray.
1.2) Quantitative polymerase chain reaction Q-PCR will be used for confirmation of virus gene expression.
1.3) Immortalized cell lines will be developed to isolate virus and elucidate links between virus and host cell gene expression.
In Aim 2), we will elucidate genetic factors of susceptibility and the dysregulation of the host defense system. Specifically, we will determine:
2.1) PBMC gene expression of 88 human genes previously confirmed as being differentially expressed in CFS
2.2) Serum chemokine and cytokine profiles using multiplex suspension antibody arrays on a Luminex platform
2.3) HLA, KIR genotypes and whole genome SNP profiles
2.4) Defects in the type I Interferon signaling pathway.
In each subaim both cohorts will be compared to normal and disease controls using specimens of serum and PBMC taken at multiple time-points from individual patients and taken from our unique and extensive sample repository.
• Will provide information necessary for development of treatment and diagnostic strategies for distinct subgroups of CFS patients,
• And may identify novel virus associations, genetic signatures, and biomarkers, which can predict the development of MCL, thus enabling use of preventive therapeutics.”....