Ian Lipkin Gets ME/CFS Grant – and So Do Others: the NIH Grants of 2015

Ian Lipkin gets a big grant. And so did some others. (Could the IOM and P2P reports have prompted this little flurry of interest?) Check out all the active NIH chronic fatigue syndrome grants I could find. ME/CFS needs many, many more grants, but anyone looking at these grants will be struck, particularly in the larger ones, by the degree of complexity present. When the NIH grants it really grants. While you’re checking these grants out envision this list being ten or more times longer. That’s what’s available when the NIH really funds a disease, and that, of course, is what disease that has the kind of impact ME/CFS does, deserves. Note that seven of the grants have an exercise component.. New Grants ​Ian Lipkin Finally Gets His Grant (or at least part of it): Microbial Immunity and Discovery in ME/CFS “I think the microbiome is going to be where the action is [in ME/CFS]… I am really eager to pursue that work.” Ian Lipkin​ It apparently took three tries but Ian Lipkin’s perseverance finally paid off. On Aug 14th he and Mady Hornig were awarded a $766,000 grant to study the gut microbiome in ME/CFS. The grant is not the whole shebang; however – or even close to it. It was is a one year grant that will allow them to collect samples. It does not provide any money to test the samples. In fact it does not, from my understanding, provide enough money to collect all the samples. An extra 250 K that has been provided by an anonymous donor and by the CII will allow them to collect all the samples. After they have completed the sample collection they will apply for more funding. Lipkin’s goal is to examine bacterial, fungal and viral microflora in the throat, lower intestinal tract and blood several times over the year in patients from six ME/CFS clinics. It will also include a small exercise component.

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NIAID – I

Do Your Immune Cells Have Post-Exertional Malaise?

Maureen Hanson has seemingly come out of nowhere to score several big ME/CFS grants, including earlier XMRV and gut grants. Prior to her work on ME/CFS her only NIH grant was for a long running RNA in Plants (yes – plants).

First she scored a major XMRV grant and then a smaller R21 microbiome grant, and now another R21 project, still slated to last for three years.

She and another researcher – Campagne – will be looking at a fascinating question: do the mitochondrial problems believed present in ME/CFS extend to the immune cells? These Cornell researchers will be examining a host of energy related features (basal respiration rate, maximal respiration rate, ATP synthesis rate, spare respiratory capacity, basal glycolysis rate, maximal glycolysis rate, and glycolytic reserve) before and after stimulating B, T and NK cells. My guess is that the immunne cells will look OK prior to stimulation and become quickly depleted of energy – after stimulation: i.e. even our immune cells will have PEM.

That, of course, would fit with the natural killer and T-cell dysfunction seen, the significant immune exhaustion the Lipkin/Hornig CFI study found in longer duration patients, and, of course, with the aerobic exercise findings.

Her past history in plants aside, this Cornell researcher is definitely in the ME/CFS NIH pipeline now and doing well.

We’re not done with Hanson, though. She also working with Fabien Campagne (lead researcher) to use state of the art deep sequencing and bioinformatics to assess gene expression of three biggies in the immune system: the B, T and NK cells.

Bearing Down On Immune Biomarkers

First they will characterize the mRNAs and microRNAs in the immune cells of ME/CFS and healthy controls. Then they will assess whether the differences they find shows up in the proteins. Since the proteins do the actual work of the cell, they are where the rubber meets the road in the body. If they can tie differences in gene expression to different levels of proteins in the body – they have the makings of a strong biomarker. If it all works out they’ll be creating some biological diagnostic algorithms; i.e. x plus y plus z in a blood test equals ME/CFS. That, of course, would be a big breakthrough

This project is slated to end in 2018. Things appear to be looking up for ME/CFS at the NIAID; both studies were funded by them.

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NIAID – III

Getting Sliced and Diced During Exercise

Lubov Nathanson -another researcher I’ve never heard of – leads this intriguing exercise study at Dr. Klimas’ Nova Southeastern University Institute. This study will dig much deeper into immune cells called PBMC’s that were gathered in an earlier study at before, during and after exercise.

The group’s prior findings suggested that the genes in these patients PBMC’s were getting sliced and diced during exercise. They believed these broken up genes might be causing inflammation, immune problems, etc. They’ll be looking for these never before identified gene transcripts in hopes of finding a biomarker and establishing what the heck is going wrong during exercise, as well as assessing methylation levels.

This brand new study funded by National Institute of Neurological Disorders and Stroke (NINDS) will run through 2018

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NIAID – III

NINDS – I

The EBV ME/CFS Hypothesis Gets Its Big Shot

If I have it right, the hypothesis goes something like this. Epstein-Barr Virus – the biggest, literally – virus in the world is actually not doing so well in ME/CFS patients. Every time it tries to replicate it fails. It should ultimately build a nice capsule to house itself in but for some it never gets to that point. It’s basically broken but because it’s broken it keeps pumping out proteins that leak into our bodies.

Our immune systems – used to dealing with the antigens on the outer surface of the virus – goes bananas when it sees these unusual substances and produces the elements of sickness behavior such as fatigue, cognitive problems and anxiety. Furthermore during periods of stress – stress probably being the water many people with ME/CFS swim in anyway – EBV reactivates or tries to – and pumps out even more of these suspect proteins.

This is a big 5 year study that looks like it’s going to cost over $3 million and NIAID is going to foot the bill.

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NIAID – IV

NINDS – I

Younger Redux

This is Younger’s much expanded followup study to his wildly successful earlier effort suggesting that leptin may be the key immune driver behind this disease. This was a grant, quite frankly, waiting to be funded. Not funding it would have been a travesty.

Younger will examine as many immune factors as he can in 70 ME/CFS women and 40 controls over 25 days. Each day the participants will note their symptom severity. He’ll attempt to develop an immune model that explains the fatigue occurring in ME/CFS, identify immune subsets and identify how immune factors work together over time to produce ME/CFS.

This big ROI grant is slated to last for four years and is being funded by the NIAID.

INSTITUTE WATCH

NIAID – V

NINDS – I

Continuing Grants

We welcome a new ME/CFS researcher to the fold with this study. Roxana Moselhi of the State University of New York at Albany is collaborating with the Simmaron Research Foundation and Dr. Peterson to do genetic, immune (particularly EBV) and epidemiological (family medical history) work not just in ME/CFS patients but in their relatives and in healthy controls and their relatives. The study seeks to help determine if ME/CFS is an autoimmune disorder (featuring antibodies to Epstein-Barr Virus (EBV)) with an hereditary component. Non-Hodgkins lymphoma is a component of it.

Tying EBV to autoimmunity to lymphoma – now that would be an eye-opening result

This NAIAD funded R21 study runs through 2016

INSTITUTE WATCH

NIAID – VI

NINDS – I

The Men Get Their Due

Gender Differences in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Mary Fletcher will continue her big RO1 grant examining how men with ME/CFS differ in their response to exercise than women. She’s going to measure the response of their genes, immune cells and chemical responses to exercise. She will also examine the regulatory pathways concerned with “latent viral expression:” i.e. herpesivruses…They expect to find significant differences between men and women with ME/CFS that will ultimately result in different treatment approaches. You may remember that the team is focused on identifying biomarkers they can tweak up or down in time (i.e. – identify a string of treatments done consecutively) one treatment then another) to shift ME/CFS patients systems back to health.

The Klimas team’s focus on doing treatments in the right order was recently underscored by a groundbreaking study indicating that immune enhancing drugs can actually suppress the immune system if the immune system isn’t prepped for them first. This study – signed off by Vicky Whittemore of NINDS, demonstrates that NINDS is willing to take on immune studies.

INSTITUTE WATCH

NIAID – VI

NINDS – II

Dr. Klimas recently said, if I remember correctly, that she oversaw the grant applications for the last SEP. She had been on at least one SEP several years before – and reported then that she was disappointed by the lack of applications. This time, however, she said she was pleased at the applications that came in. (It’s not clear if she was on the panel that pushed forward Lipkin’s grant application.)

Baraniuk’s Brains #1

Baraniuk will be examining “exosomes” in ME/CFS. Exosomes are “multi-protein intracellular complex capable of degrading various types of RNA” (Does that clear everything up?). They are often associated with autoimmune diseases.

Baraniuk will be examining the miRNA and protein expression of these exosomes using PCR in the cerebral spinal fluid of ME/CFS patients. Baraniuks’s spinal fluid proteome expression study about ten years ago was successful but he asserts that this search will be able to identify more proteins plus 380 miRNA’s. (miRNA’s regulate gene expression.) By the end of this study he hopes to have identified significant sources of problems in the brain associated, he believes probably the microglia, astrocytes and other cells.

This is a continuing project slated to end next year that was signed off by Vicky Whittemore of NINDS.

INSTITUTE WATCH

NIAID – VI

NINDS – III

Baraniuk’s Brains on Exercise

James Baraniuk of Georgetown University earlier showed that the brains of GWS patients undergo significant changes when they exercise. Given the symptom similarity between GWS and ME/CFS, he proposes the same thing will happen to people with ME/CFS.

In this five year, NINDS funded study ending in 2018 Baraniuk hopes to be able to use the altered neural pathways he finds to uncover subsets in ME/CFS.

INSTITUTE WATCH

NIAID – VI

NINDS – IV

Dubbo Goes to College

Ben Katz is going to do for college students what Andrew Lloyd did for people infected with pathogens in Dubbo, Australia; try to find out what’s causing people with an infection to come down with ME/CFS.

This impressive study seeks to enroll everyone on the Northwestern University campus into it, and then follow everyone who comes down with infectious mononucleosis – a known trigger of ME/CFS -for twelve months. They will examine biological (autonomic dysfunction, cytokines) and pyschological factors (coping skills, stressful life events) functioning. At the end they hope to determine risk factors for coming down with ME/CFS and biological factors that perpetuate it.

This expensive study ($700,000 this year) funded by NIAID (immune Institute) runs through 2018. NIAID funded it.

INSTITUTE WATCH

NIAID – VII

NINDS – IV

Lenny Jason’s population sampling study will determine the prevalence of pediatric ME/CFS, and the extent of orthostatic intolerance present. It will also examine the degree of “central” or brain based fatigue and cognitive impairment present by putting the kids on a tilt table and asking them to do a mental task. If the kids utter failure on the cognitive tests correlates reduced blood brain flows, then Lenny will have provided a biological reason for the cognitive problems found in kids with ME/CFS.

This study – already underway for several years – ends in 2016. The Office of the Director funded it.

INSTITUTE WATCH

NIAID – VII

NINDS – III

Office of the Director – I

Your Gene Expression On Exercise

Exploring host gene expression during post-exertional symptom flare in ME/CFS

Another new researcher – this time from Canada – enters the fold in this exercise study. David Patrick, who works at Canada’s version CDC , is apparently a big cheese in Canada. His exercise physiologist met with Staci Stevens and Chris Snell of the Workwell Institute regarding the two-day exercise tests. He reportedly entered a skeptic and came away a rather stunned believer.

Now,Patrick aims to take the deepest look yet at what happens to the expression of our genes during exercise. He will use next generation sequencing to examine the expression of more genes (particularly immune genes) in more detail than has ever been done before.

Another NINDS funding study, this University of British Columbia project began in 2014 and will wrap up next year.

INSTITUTE WATCH

NIAID – VII

NINDS – V

Office of the Director – I

Probing the Exercise/Muscle/Fatigue/Pain Connection

Roland Staud – better known as a fibromyalgia researcher – continues a long-running five- year grant on the effects of exercise on muscle metabolites on fatigue and pain in ME/CFS. One paper published from this study suggested that metabolites produced by the muscles of ME/CFS patients (but not the muscles of the healthy control patients) were producing pain and fatigue in ME/CFS. Either the muscle metabolites are over activating sensory nerves or there are simply more of them. My understanding of the study suggests the first.

This study – funded by the National Institute of Nursing Research (NINR) ends in 2017.

The INSTITUTE WATCH

The race was between the immune and neurological Institutes with NIAID pulling out a win with seven currently funded studies to the NIND’s five.