A year and a half after it awarded $157 million in grants to establish 10 proteomics technology development centers, the National Heart, Lung, and Blood Institute announced last week that it will follow up this investment by dishing out another $25.5 million for the establishment of a set of clinical proteomics programs (click here for the RFA, see PM 10-14-02, PM 10-21-02).
The funding, to be spread out over four years — beginning with $4.5 million in FY 2005 — will support three to five multidisciplinary teams. The teams will be charged with designing panels of diagnostic and prognostic protein biomarkers for heart, blood, lung, and sleep disorders. They will not be involved in basic biomarker discovery, but will instead draw upon groups of markers that have already emerged from the discovery process and validate the markers in a high-throughput manner on clinical samples. The centers will also be expected to develop standards for sample handling. Each center will be responsible for gaining access to its own clinical sample set. “They have to prove they have expertise across the board,” said Pothur Srinivas, program administrator for the initiative.
According to Srinivas, the most important factors that the NHLBI will consider when awarding the grants are the infrastructure that applicants have available for the validation process and the strength of the multidisciplinary team. “They have to have the infrastructure in there so that they can process samples in a high-throughput fashion, and also … the capability of technology development for clinical assays,” Srinivas said. “[A]nd since they have to validate it in a sample set from humans, they have to be able to come up with all the algorithms, calculations, [and] epidemiological studies.”
Srinivas said that the main motivation for putting out the new RFA was to ensure that the $157 million already invested in the technology centers did not go to waste. “Because we’ve already put money into the proteomics centers, we want to be able to leverage it,” Srinivas said. “We want to be able to maintain the investment so we can get something tangible out.” He said that the NHLBI was following the advice of an “expert panel,” which suggested that the next step in the “blooming” proteomics field was clinical development.
The grant announcement came a few months after the institute held a workshop in Washington “that focused almost completely on clinical proteomics,” according to Alexander Kurosky, principal investigator of an NHLBI-funded proteomics center at the University of Texas Medical Branch in Galveston. But the impetus for the new initiative preceded the workshop and the technology centers, said Tom Kodadek, PI of the NHLBI proteomics center at University of Texas Southwestern Medical Center in Dallas. “When we first did this proteomics program, NHLBI asked me at the inception to write up a white paper for what the whole proteomics program should be,” Kodadek said. After recruiting other scientists at that time to form an initial panel on the subject, “in the course of that discussion, one of the things that was obviously on the mind of NHLBI was whether they shouldn’t make part of the proteomics program a direct clinical link, or whether they shouldn’t start parallel centers in direct clinical proteomics. And our overwhelming feeling of everyone on my board two to three years ago was that it wasn’t quite time yet, simply because the technologies weren’t that good yet,” Kodadek said.
But Kodadek and Kurosky both suggested that the NHLBI later found the inspiration to finally set up clinical programs in the recent relative successes of the NCI-FDA clinical proteomics program. “I think what’s really stoked everyone’s interest is all this work going on in cancer — especially Petricoin and Liotta at the NCI recognizing these signatures,” Kodadek said. Although Kodadek said he felt it was still “a little early” in the development of the proteomics field to be jumping into the clinical realm, he added that, given the financial motivation of the NHLBI and the recent increase in excitement over biomarkers, “it’s not unreasonable to start this.”
Existing NHLBI technology centers can apply for the new clinical proteomics grants, and can offer their own markers and methods that they developed for further clinical analysis under the auspices of the new programs, Srinivas said. The selection process will be open, however, and new applications will be reviewed separately from the existing technology grants. Both Kurosky and Kodadek said they are planning to apply for the new grants, and that they are talking with clinicians to develop a team.
Srinivas said the program will be evaluated on a yearly basis to see how it is functioning, and that further proteomics funding was a possibility, depending on how things go. The NHLBI will also select one coordinating center that will set up yearly meetings among the funding recipients to share successes and failures. Each application must include a proposal for such a center, Srinivas said.
The NHLBI is not the only NIH institute to focus its recent proteomics funding on validation of clinical samples: the National Institute of Diabetes and Digestive and Kidney Diseases announced on March 18 that it would earmark $1 million in FY 2005 for the development of proteomics- or meta-bolomics-based diagnostics for type 2 diabetes (click here for the PAR, see PM 3-26-04).
The NIDDK will provide its own human plasma samples for validation studies on any biomarkers found, according to the RFA.
The NHLBI will not provide such samples.
The application deadline for the NHLBI clinical proteomics program grants is Oct. 15 of this year. Grants are expected to be awarded in July 2005, according to the RFA.