NIH awards total of $1.3m to Lipkin, Klimas, Hanson

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Sasha

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Good news! Good news!

Spotted by Kathryn Stephens on FB.

Lipkin & Hornig: "Microbial Discovery and Immunity in ME/CFS"
National Institute of Allergy and Infectious Diseases
$766,000

NIH said:
DESCRIPTION (provided by applicant): Myalgic Encephalomyelitis/Chronic Fatigue Syndrome is an idiopathic disabling disorder characterized by persistent, unexplained fatigue in association with impaired memory or cognition, muscle or joint pain, headache, sore throat, tender lymphadenopathy and night sweats.

The prevalence in the US is estimated at over 200 cases/100,000 population with annual medical care costs of $24 billion. There is no specific diagnostic test or treatment.

Although the majority of cases are sporadic, there are reports of geographic and temporal clusters of CFS and many subjects report a viral prodrome and symptoms consistent with an infection.

Efforts to identify causative agents have yielded inconsistent results and in some instances culminated in false leads that polarized the patient advocate and biomedical research communities, led to inappropriate allocation of resources and placed patients at risk for inappropriate therapeutic interventions.

This project will test the hypothesis that CFS cases and controls differ with respect to bacterial, fungal or viral microflora in the oropharynx, lower gastrointestinal tract and blood in a well-powered study, using rigorously characterized cases and controls and state-of-the-art methods for microbial surveillance and discovery.

Our proposal builds on the foundation established during the NIAID CFS multicenter study of XMRV/pMLV. It includes the expert clinicians who led work at the original six sites, thereby ensuring credibility within the scientific and CFS patient and advocacy communities and access to a network within which follow-up studies and translational research can be readily pursued.

The laboratory team has extensive experience in infectious disease epidemiology, microbial discovery and de-discovery, as well as in the development of serological assays and animal models needed to test for causal relationships and investigate pathogenetic mechanisms.
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Klimas: "Genomic approach to find novel biomarkers and mechanisms of CFS/ME"
National Institute of Neurological Disorders and Stroke
$320,000

NIH said:
DESCRIPTION (provided by applicant): Current management of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) relies solely on symptom management to improve quality of life but does not address the underlying mechanisms of disease onset and progression.

In an effort to provide insight into the key biological targets involved CFS/ME presentation, the main objective of this research proposal is to identify novel biomarkers and therapeutic targets of CFS/ME and provide insight into disease onset and progression.

This research proposal aims to use Peripheral Blood Mononuclear Cells (PBMC) from patients recruited for our recently NIH funded research.

These PBMC have been isolated from CFS/ME patients and matched healthy controls at three time points - before exercise challenge, at the peak of effort (VO2 max) and four hours after the peak effort. Specific Aims of this proposal include:

Specific Aim 1. Identify metabolic pathways affected at CFS/ME and possible regulatory RNAs. Based on our previous findings, our hypothesis is that unknown transcripts and alternative splicing events regulate changes in expression of genes responsible for inflammatory response, immune system processes, leukocyte migration, and regulation of cell development. This is leading to changes in CFS/ME disease activity.

We aim to expand our research efforts, by using an RNA-seq approach to identify the abundance of transcripts, discover new splicing events, and presence of novel transcripts.

This will allow identifying biomarkers as a result of differentially expressed transcripts and alternative splicing and non-coding RNAs to establish a set of CFS/ME specific candidate transcripts. We will then validate them using NanoString Technologies' nCounter system and create a panel of transcripts to potentially be used in the diagnosis and management of CFS/ME.

Specific Aim 2. To investigate possible mechanisms of transcriptional regulation in CFS/ME. To better understand causes of changes in gene expression in patients with CFS/ME, we aim to identify changes in copy number variation (CNV) and genomic DNA methylation.

We will use Agilent SurePrint G3 Human Genome CGH+SNP microarrays to determine CNV in CFS/ME and identify a set of CFS/ME-specific candidate CNVs. We will use Illumina Infinium Human Methylation450 BeadChip microarrays as well as real-time probe-based PCR to evaluate differences in the methylation patterns between CFS/ME patients and healthy controls.

We will combine the results of RNA-seq, CNV and methylation assays and research correlation to determine possible mechanisms of transcriptional regulation involved in CFS/ME, which will lead to the better targeted therapeutic intervention.
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Maureen Hanson: "Cellular Metabolism in Lymphocytes in ME/CFS"
National Institute of Allergy and Infectious Diseases
$237,000

NIH said:
DESCRIPTION (provided by applicant): The profound fatigue experienced by patients with encephalomyelitis/chronic fatigue syndrome (ME/CFS) has led to the theory that energy metabolism may be dysregulated, but discordant results have been obtained in prior studies of mitochondrial function.

Hallmark symptoms of ME/CFS) in addition to fatigue are headache, muscle aches, malaise, swollen lymph nodes, and sore throat, all characteristics of an inflammatory process.

Differences between various properties of lymphocytes in ME/CFS cases and controls are well documented, but the basis of the alterations is not understood. Lymphocytes require both glycolysis and oxidative phosphorylation to carry out their immune functions.

Usage of these two primary pathways for energy generation is known to change between resting and activated cells in healthy individuals. Impaired functioning of energy metabolism in lymphocytes could be either the cause or consequence of the unknown damage to cellular processes that occurs in ME/CFS. In order to investigate the efficiency and usage of glycolysis and mitochondrial respiration in ME/CFS immune cells, we will assay isolated peripheral blood mononuclear cells and isolated B, T, and NK cells with the use of a flux analyzer.

We will obtain measures of basal respiration rate, maximal respiration rate, ATP synthesis rate, spare respiratory capacity, basal glycolysis rate, maximal glycolysis rate, and glycolytic reserve in immune cells before and after stimulation.

We will determine whether this information correlates with any of known aspects of the proposed cohort of ME/CFS cases and controls, which will have been characterized previously for microbiome and mitochondrial DNA composition.
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S

Sasha

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I must say that this is all a bit of a weird development after CFSAC in which we were being told that there were few applications to the NIH and that they were pretty rubbish.

I hope this is something to do with the involvement of the new NIH rep, Vicky Whittemore. She impressed me at that meeting with her genuine goodwill.
 
viggster

viggster

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This is great news. As for "chump change," ask any biomed lab researcher if they'd like $760,000 from NIH. Lipkin now has $1.5 million, about half from crowdfunding and half from NIH, to do a thorough study, and he'll be using the samples collected during the XMRV search a few years ago. This is a very wise thing to do - leverage this biobank. When Dr. Collins wrote to me a few weeks ago, he mentioned the biobank as a resource and implied it would be used again.
 
Scarecrow

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Sasha said:
Bit of an odd combo of topics. I wonder if this is another case of a scientist having a loved one who is sick and deciding to apply their skills in a new area.
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It's interesting that one of her areas of ME/CFS interest (gut / microbiome) is complementary to Hornig & Lipkin while the other for which she has got the grant (gene expression at baseline and after exercise) is complementary to Klimas.

Edited to add: yes, vegetables and CFS! That is odd. Hmmmm.
 
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