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NCGR CEO Stephen Kingsmore on $2.7M NIAID Sepsis, CAP Diagnostics Project

Stephen Kingsmore
President and CEO
National Center for Genome Resources

Name: Stephen Kingsmore

Position: President and CEO, National Center for Genome Resources, 2004 — the present

Background: Chief Operating Officer, Molecular Staging, 1999 — 2004

Vice President of Research of CuraGen Corporation, 1997 — 1999

Education: MB, ChB, and BAO in medicine, Queen's University of Belfast, 1985.

Last week the National Center for Geonome Resources said it had been awarded $2.7 million by the US National Institute of Allergy and Infectious Disease for the Community Acquired Pneumonia & Sepsis Outcome Diagnostics program, which involves: NCGR; Duke University Medical Center in Durham, NC; Henry Ford Hospital in Detroit; Indianapolis-based Eli Lilly; the Indiana Centers for Applied Protein Sciences in Indianapolis; and ProSanos of La Jolla, Calif.

The project aims to create new diagnostics for sepsis and CAP, which are the number 10 cause of death and the number one cause of death from infectious disease in the United States, respectively. Both are also thought to be excellent areas for pharmacogenomic techniques to guide therapy through prognostic applications and in predicting drug response, and the NCGR is already involved in a separate project involving both areas.

Pharmacogenomics Reporter spoke to Stephen Kingsmore, the NCGR president and CEO, for more detail on the project, the technologies it will use, and the diagnostics that may come out of it.

How will the award money be put to use?

It's a grant mechanism where NIAID exercises some control over what we do, so it's not one of these awards where they hit the button and it automatically goes into your account. I'm a PI on it, and NCGR is the primary institution, but the funds are dispersed amongst all of the partners. With this being a clinical study, the majority of the funds goes to accrue the patients and collect the clinical data, so Duke University and Henry Ford are the biggest beneficiaries.

What role does NCGR play in this?

We put together this consortium, so it's that role of being the '-omics' integrator, where we're going to have a lot of very high-quality clinical data — proteomic data in the future, some transcriptomic and genetic data. And we'll be providing some bioinformatic support for data analysis, but also just project management.

The thing is, to do excellent clinical studies and to do excellent -omics studies are incredibly different skill sets, and so there's this need for a kind of matchmaker thing, where you have people who can speak both languages.

You have another project involving community acquired pneumonia and sepsis — is there any overlap of the two projects?

Well, we have a partnership with DeCode Genetics and the University of New Mexico to identify genes that affect outcome in a number of infectious diseases, like influenza. So, there's some overlap there, but there's no collaboration between the two efforts right now. That may change in the future, but right now they just happen to have similar aims.

We'll see — it would seem to me that, as we identify candidate genes, it would be very interesting to compare them in this new cohort.

You mentioned proteomic data — what is the full spectrum of data you will be collecting?

Well, the award to date allows us to do mass spectrometry to collect proteomic data on plasma, but in addition — if you remember the old Molecular Staging partnership with [Eli] Lilly from a couple of years ago, this sprang out of that. What we had done there was to use protein chips to survey about 150 cytokines and other biological mediators in serum and plasma in the PROWESS patients. That's the set of patients with severe sepsis that were used in the approval of the drug Xigris for severe sepsis.

So what we're going to do here, in addition to mass spec, is also to follow up on a whole bunch of those particular proteins using conventional amino acid technology to see whether they pan out in early stage sepsis and in pneumonia. Because the PROWESS study was limited to people with very severe sepsis, this now is a study looking at people with the earliest stages of sepsis, and if you want a diagnostic, you want it to be useful early in disease, you know? So we found some interesting mediators — we'd like to take them back to the earliest stages to see whether they are still of utility. If they are, then they probably have great diagnostic value.

Which platforms are going to be put to use in this part of the study?

We're going to be using Incap's mass spec technologies for the shotgun mass spec studies, we're going to be using Prosanos' clinical registry platform. For the immunoassay platform, we haven't made a selection yet. We've got money banked for that, but we haven't made a choice. And you know, right now there's a bit of a shakeup in terms of multiplexed immunoassays, so we're just going to wait and see. For sure there'll be some good platforms available in year three, when we need to make that choice.

This project aims to create molecular diagnostics — how is that planned to happen?

We're going to need to have diagnostic partners. Right now, we have three commercial entities involved in this: Prosanos, which runs clinical trial registries; Lilly, which is a pharma; and Incaps, which is a biomarker development group. So, we don't have a diagnostic partner, and that's gong to be one of our goals as we proceed, to have one or more diagnostic partners be part of this effort.

When do you hope to recruit a diagnostic partner?

We've had discussions with a couple already, so my goal would be over the next year, to do that. I'd really like to do that as quickly as possible, because if you're going to meet FDA requirements for this study to be useful in a submission, we really need to have that resolved up front, rather than bootstrap it on after the fact.

How many patients will be in the study?

Right now we're talking about 400 patients — 350 adults and 50 kids. The disease is different in kids from adults. So we have some goals to expand that — we're looking at two diseases, community acquired pneumonia and sepsis. We need more community acquired pneumonia patients. And we need more kids. So this is sort of step one. We want to add expression profiling — that's not funded in this. This is a good starting point, and we hope to add additional funds.

We will be collecting the samples for expression profiling — we'll have them archived, we'll have all the clinical variables, so when we get the funding we'll go ahead and pull the trigger on that.

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