A new research landscape emerges in America

Things are changing in the US for ME/CFS research as four new collaboratives set up and get to work.

In September last year, the National Institutes of Health (NIH) announced $35 million of funding to establish three new ME/CFS research collaboratives and a supporting data centre. Since then, the Open Medicine Foundation (OMF) has helped to establish a fourth research collaborative, at Stanford, committing $2.4 million for the first two years. It aims to fund the collaborative at similar levels until the work is complete.

So that’s four new collaboratives based at leading institutions, using top researchers and clinicians and backed by a substantial amount of cash. The collaboratives will be using cutting-edge technology and large, well-defined samples of patients. This adds up to a game-changer for biomedical research in the US, putting it way ahead of the rest of the world.

The NIH-funded collaboratives are:

  • The Center for Solutions for ME/CFS headed up by Dr Ian Lipkin and based at Columbia University in New York City.
  • The Cornell ME/CFS Collaborative Research Center led by Dr Maureen Hanson at Cornell University, Ithaca, New York State.
  • The Jackson Laboratory ME/CFS Collaborative Research Center led by Dr Derya Unutmatz and based in Connecticut.

And the supporting centre for the NIH groups is the Data Management and Coordinating Center run by Dr Rick Williams at the Research Triangle Institute in North Carolina.

Each NIH-funded collaborative has been awarded around $10 million each over five years, with around $5 million for the data centre.

NIH director Dr Francis Collins said the collaboratives would “lead to knowledge about the causes and ways to treat people affected by this mysterious, heart-breaking, and debilitating disease”. All the collaboratives have said they aim to understand the mechanisms of the illness in order to develop treatments and to identify biomarkers.

  • The ME/CFS research collaborative at Stanford University will be run by Dr Ron Davis and funded by OMF through donations it receives from patients and supporters.

The four collaboratives

The Center for Solutions for ME/CFS, led by Lipkin, will investigate whether the bacteria, viruses and fungi of the gut microbiome are driving the illness.

Gut microbiome computerThe microbiome could lead to a disease process by firing up the immune system or even by producing chemicals (metabolites) that then get into the blood, where they would affect the nervous system. The collaborative will use state-of-the-art techniques including DNA-sequencing to look at gut microbes, and metabolomics to explore the chemical fingerprints left in the blood by cells or coming from the gut microbiome. The team will also investigate the immune system, including examining antibodies to identify any past infection that might have triggered problems.

The research team will look to see how exercise affects both gene expression and metabolites. The group will mine clinical data to try to identify different types of patients and will develop a mobile app to track patients’ symptoms over time. The collaborative has an impressive clinical team that includes Drs Anthony Komaroff, Jose Montoya, Lucinda Bateman, Susan Levine and Dan Peterson.

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Dr Maureen Hanson

The Cornell ME/CFS Collaborative Research Center is combining an exercise challenge with a wide range of techniques to probe what’s happening in ME/CFS. Dr Shungu, who is a professor of physics and radiology, will use brain-imaging techniques. He’ll be looking for signs of neuroinflammation (following up this intriguing finding from 2014), mitochondrial problems and oxidative stress.

Dr Hanson, who leads the Cornell collaborative, is heading down an entirely new path, looking at extracellular vesicles. These are little sacs of molecules – including proteins, hormones and RNAs – that cells release and that fuse with other cells. Vesicles are released in response to exercise and could be contributing to disease symptoms. The team will also probe immune-system functioning by measuring gene expression in different types of immune cells in the blood.

All of these different approaches will be applied both before and after exercise, to identify any differences linked to the cardinal ME/CFS symptom of post-exertional malaise. Professor Betsy Keller, an expert in using the two-day exercise challenge, will co-lead the clinical set-up; expert physicians Dr Susan Levine and Dr John Chia are on the clinical team.

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Dr Derya Unutmaz (Photo: Jax ME/CFS)

The Jackson Laboratory ME/CFS Collaborative Research Center is led by Dr Derya Unutmaz. As the name suggests, this collaborative is at the Jackson Laboratory, which might not be well known to patients, but is a well-established, independent, non-profit biomedical research institution that’s been around since 1929.

This collaborative will look to see if the interplay between the microbiome, the immune system and metabolism could be driving the illness. The team will use highly advanced analysis combining clinical and biological data to look for connections and will use the company Precise.ly to develop an app-based patients’ portal to collect and analyse data. Patients will come from Dr Cindy Bateman’s clinic in Utah.

While there are many similarities with the Lipkin project, Unutmaz is likely to approach some things in a different way. He’s an immunologist with experience of chronic inflammatory diseases and a focus on T cells in particular.

Research triangleThe Data Management Coordinating Center will be run by Dr Rick Williams of the Research Triangle Institute in Durham, North Carolina, and Dr John Rowe of Johns Hopkins University. The centre will pool and manage data from all the NIH-funded collaboratives, allowing data from different studies to be compared and combined: the data centre will be providing statistical tools for analysis. The centre will also be responsible for engaging with the wider research community, presumably making the data more widely available.

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Dr Ron Davis

The ME/CFS Collaborative Research Center at Stanford is led by Dr Ron Davis. One of his impressive team, Dr Mark Davis, has already found clear evidence of T cell clonal expansion, though the findings are yet to be published. Mark Davis believes that the clonal expansion is being driven either by the T cells’ reaction to foreign invaders, such as a virus, or by a misguided response to “self” in the form of an autoimmune response.

He will continue to try to track down exactly what it is that’s firing up the T cells, using some very clever molecular detective-work. The collaborative will also expand its in-depth genetic and molecular study of 20 severely ill patients to include a wider group, to validate and extend the initial, tentative findings.

Finally, there’s Ron Davis’s goal of creating an affordable, accurate blood test for diagnosis and drug-screening, starting by developing the promising nanoneedle technology.

Collaboratives-final-map
Four collaboratives and a data centre

Concentrating firepower for more reliable results

There’s a striking overlap in the approaches used by the different collaboratives, with two of them using an exercise challenge, two focussing on metabolomics and the microbiome, and all of the groups majoring on the immune system.

The overlap is no coincidence, at least not for the NIH Collaboratives, says NIH Director Collins. Referring to the dead end of XMRV back in 2012, he said, “We want to see immediately if something looks like it’s promising, is it promising really, or another false positive? We’ve had too many of those and we don’t want to make that mistake again.”

Ruling out things that appear good but are not robust, as exemplified by the rituximab trial, is essential for progress in any scientific field.

Patients on board

All of the new collaboratives are working to involve patients. Lipkin’s team has involved the Microbe Discovery Project, #MEAction and the Solve ME/CFS Initiative (SMCI). Cornell also has the SMCI on board as well as patient-activist Erica Verillo. The Jackson group has activist Mary Dimmock, is closely linked to #MEAction and also runs a blog.

Ramping up ME/CFS research?

The NIH is funding its collaboratives and support centre to the tune of $35 million over 5 years, amounting to an increase in NIH funding for ME/CFS research of $7 million a year. That’s a lot less than many patients had expected when Collins pledged to “ramp up” funding for the disease, and does not seem enough given that ME/CFS is poorly understood and inflicts so much suffering on so many.

While the sums invested in the collaboratives aren’t impressive, the quality of the research programmes is. The NIH must have spent close to $100 million on ME/CFS research over the last two decades without having very much to show for it. That could be one reason why the NIH has argued that what’s needed most is to increase the capacity of the field to do high-quality research – and the collaboratives, including the OMF-funded one at Stanford, should do just that.

The groups bring in new talent. All are led by researchers relatively new to the field and are full of scientists who have honed their expertise in other areas, bringing new insights and skills to ME/CFS.

These new centres also bring researchers together to form a critical mass, and the three NIH centres are themselves working together, with plans to collaborate on at least one joint project. Critically, each collaborative also has a strong clinical aspect to ensure they have large cohorts of well-diagnosed patients that will surely be an invaluable resource for the future.

All of these things will increase the capacity of the field to do more high-quality research. That should mean more successful grant applications and more funding.

At worst, the findings that emerge from these comprehensive studies might simply enable the teams to rule out lines of enquiry, enabling the field to move on.

But with a fair wind, the centres could make real, substantive progress in finally understanding the biological basis of the disease, opening up the way to the development of treatments and diagnostic biomarkers.

The collaboratives are creating a new and more impressive research landscape in America. It’s one that should give ME/CFS patients everywhere real hope for progress.

Update: the 5th Collaborative

There will be a fifth collaborative, across the border in Canada. The Canadian Institutes of Health Research has invited researchers to apply for a grant of up to C$1.8 million (US$1.4 million) to form a new collaborative that will work with the three NIH collaboratives on a joint project and share the NIH data centre. The winning bid will be announced in July. Thanks to Cort Johnson for mentioning this in the comments below  

Thanks to Jennie Spotila whose meticulously researched blogs at Occupy ME provided much valuable information for this article.

COMING NEXT: Profiles of each of the four collaboratives

15 thoughts on “A new research landscape emerges in America

      1. jeremy bearman

        hi there simon
        thanks so much for this infographic/breakdown
        and for your efforts in this arena in general
        i have donated and fundraised for 20 out of my 24 years of being ill and although, it may look slightly impressive, that the nih have started funding these centres, if you look at your organogram and realise that represents most of the govt sponsored activity in a massive wealthy and research intensive country like america, its actually dreadfully disheartening. why did the nih cruelly close down prof benjamin natelson’s wonderfully productive centre all those years ago. the whole team have disbanded and essentially moved on. right here and now in 2018, researchers have privately confided in me that the funding climate re getting grants approved by the nih for research into this illness, is as bad as it has ever been. activists have been prostrating themselves before the nih and various committees for decades just to tread water and not have the situation regress.

        so these enhancements are mostly academic in the sense that the scale is not adequate to lead to a relatively rapid discovery of biomarker and development of treatment. assuming that a treatment started development today, it would still take 10 years to come to market it if succeeded. all of these people involved in the centres you depict, are really marvelous and highly committed the problem is with the people controlling the purse strings at the nih. their allocation of funds is a clear indication of how little they care about redressing decades of shocking neglect of funding and physician education.

        if we as 17 million plus, patients around the world, dont step in to help research efforts, then we shouldnt expect much to happen other than more false promises from the nih and its subsidiaries
        if each patient gave only 10 dollars a year, that 170 million that could go towards research. that kind of money could really turn things around without bankrupting already financially distressed patients

        very nicely written article simon, but things are not looking too good for us patients

        Liked by 2 people

  1. Ross Brodie

    Great summary and very uplifting for those of us with severe ME. Hope can help you through the bad days. I want to thank the researchers for their hard work and giving us hope.

    Liked by 2 people

  2. cortjohnson

    Great summary. Loved this – While the sums invested in the collaboratives aren’t impressive, the quality of the research programmes is

    and this:

    The groups bring in new talent. All are led by researchers relatively new to the field and are full of scientists who have honed their expertise in other areas, bringing new insights and skills to ME/CFS.

    These new centres also bring researchers together to form a critical mass, and the three NIH centres are themselves working together, with plans to collaborate on at least one joint project. Critically, each collaborative also has a strong clinical aspect to ensure they have large cohorts of well-diagnosed patients that will surely be an invaluable resource for the future.

    All of these things will increase the capacity of the field to do more high-quality research. That should mean more successful grant applications and more funding.

    At worst, the findings that emerge from these comprehensive studies might simply enable the teams to rule out lines of enquiry, enabling the field to move on.

    Very nicely put!

    But with a fair wind, the centres could make real, substantive progress in finally understanding the biological basis of the disease, opening up the way to the development of treatments and diagnostic biomarkers.

    Liked by 2 people

    1. Thanks for your generous comments, Cort, means a lot coming from you.

      I think I covered the story more than six months after you got to it, So I tried to say something a bit different. Though I think you were the first to point out that the lead research has been relatively new to field.

      Like

    1. Thanks, and I really am in awe of your ability to pull together accurate detailed information. I’m sure I will be going back to your blogs as a source when I write about the individual centres.

      Like

  3. Pingback: A New Research Landscape Emerges In America – The York ME Community

  4. cortjohnson

    Ha! Simon – we all missed one:) Canada is funding a research center to collaborate with the three NIH funded centers in the U.S. – Those research centers are already having an impact!

    “CIHR is participating as an international collaborator on this NIH initiative, and will provide funding to one Canadian multidisciplinary team to participate in the ME/CFS Collaborative Project with NIH’s CRCs and DMCC. The successful Canadian team is expected to coordinate with existing initiatives in the field, to forge links with the wider community (including practitioners, policy makers and service users) and include additional partners, such as commercial or industrial representatives where appropriate. Additionally, the successful team will encourage collaboration, communication and training that will extend beyond the lifetime of the five-year grant.”

    https://www.researchnet-recherchenet.ca/rnr16/viewOpportunityDetails.do?browseArc=true&fodAgency=CIHR&org=CIHR&progCd=10866&view=browseArchive&language=E

    Liked by 1 person

  5. Vassie

    I think it’s totally amazing that WE, the patients, funded one of those centres!
    And that the Pineapple Fund added another major sum! That is so important and inspiring.

    On the other hand it says everything, doesn’t it? The government’s grants are equaled by private donations.

    Why do we have to do this ourselves? Why do we have to depend on philanthropy to get the basic research done?

    Liked by 1 person

    1. So far the Pineapple donation hasn’t all been committed to the Stanford centre, which is currently only being funded for around $5 million, roughly half of each off the N I H collaboratives. I don’t know about the US, but in the UK nonprofits/philanthropy plays a major role in funding research into specific medical conditions. Because the government generally doesn’t do enough (is particularly bad for ME/CFS).
      I wonder what we can do to get the government to give more? In the US, is it to lobby Congress? I gather this is how the N I H has been mandated to commit major firms to diseases such as HIV/AIDS.

      Like

  6. Peter

    Great overview. Although funding overall is way to small, building this infrastructure is key and very promising. Hopefully these centers will also be able to collaborate, cause we are in desperate need of optimal collaboration among clinicians and scientists. You can’t have one (centers) without the other (substantial funding), but there is reasonable hope for well conducted studies on ME. Finding the mechanisms is obviously the focus and ultimate goal, and along the way it will be another hard decade for both scientists and patients.

    Etiology and treatment are close to one, but maybe, as a mere thought, you could split 70/30. Hunting cause is priority number one, then maybe investing 30 in looking for possible soothing treatment options that could benefit and be safe in the long run. It is quite devastating that reality today, is that we really don’t have any options, any safe beneficial drug with acceptable side-effects. Maybe I’m just dreaming and asking to much, but hey, it’s worth a thought when we all know the harsh symptoms and dynamics of ME. It is worth reminding what doctor Fluge once said, think it was a couple of years ago in an intermission at a conference in US. They were impressed by all the dedicated people, at the same time coming from the field of cancer, a little surprised that there was so few initiatives regarding treatment. Again; etiology, cause and treatment can’t be separated, but I believe this is important to bare in mind. It would be very significant to patients if you could raise quality a notch or two while hunting down cause.

    Liked by 2 people

  7. Pingback: There’s a yawning gap in ME/CFS research funding. Take action. – ME/CFS Research Review

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