7,000 points of light

Sigma Life Science and Boston University awarded NHLBI grant to probe samples from Framingham Heart Study for biomarkers in cardiovascular disease

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ST LOUIS—As Sigma Life Science continues to intensify its focus on developing biological products and services, this business unit of global life science and technology company Sigma-Aldrich Co. recently announced that it has been awarded a government grant to help develop methods to measure several potential biomarkers of atherosclerotic cardiovascular disease (CVD).

The National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) will provide funding for the five-year project to Sigma Life Science under a $3,836,728 research subaward agreement with Boston University. Under the agreement, announced Aug. 5, Sigma Life Science and researchers at Boston University's School of Medicine analyze plasma samples from 7,000 participants of the NHLBI's Framingham Heart Study (FHS), one of the most prestigious clinical studies in medicine, to investigate 180 potential biomarkers for CVD.

Sigma Life Science applied for the grant three years ago after deciding to focus less on chemistry and more on biology, and to seek out academic partnerships to aid in that strategy, says George Lipscomb, market segment manager for the company.
"We went through an extensive review with Boston University and the NHLBI, and from both a scientific and operational standpoint, we ended up being the best choice for the collaboration," Lipscomb says.

Lipscomb's colleague, Dave Smoller, president of Sigma-Aldrich's Research Biotech Business unit, adds, "I think the fact that we are now the leading antibody content provider in the world now shows that we have many points of light around this area of biology when it comes to antibodies and assay development. So you might say that with this project, we have 7,000 more points of light."

The FHS is an ongoing cardiovascular study of residents of the town of Framingham, Mass. The NHLBI project began in 1948 with 5,209 adult subjects from Framingham, and in 1971, Boston University was brought on board as a collaborator. Now in its third generation of participants, the study has produced much of what is now commonly known about heart disease, such as the effects of diet, exercise and cholesterol levels.

The new project is part of a major FHS initiative called the Systems Approach to Biomarker Research in Cardiovascular Disease (SABRe CVD), which expects to identify and validate new CVD biomarkers, ultimately leading to the development of blood tests to identify individuals at high risk of heart disease and stroke.

"The fascinating thing about the Framingham study is that there is this so much phenotypic information about all of these people's lives, and you can run all of their samples and look at all the information you want," Smoller says. "It's similar to sequencing the genome of 7,000 people. As you learn more about what markers are turned on or off, you can go back into people's histories and make correlations. And as these people continue to live their lives and have good and bad health, you can continue to correlate that data to find new markers for disease and health."

Over the course of the five-year project, Sigma Life Science expects to develop antibody reagents for each identified target biomarker and incorporate the reagents into a multiplexed, high-throughput platform to measure the proteins of interest. The identification of antibody reagents specific to CVD biomarkers is expected to expand Sigma Life Science's growing portfolio of more than 38,000 monoclonal and polyclonal antibodies. In addition, the company offers 8,300 highly validated Prestige Antibodies, covering more than 6,900 human protein targets identified by the Human Proteome Resource.

The project has another potential benefit for Sigma Life Science, adds Lipscomb: "Because of the systems biology and genomic components of the study, it could also result in the design of new animal models, as well," he says. "It opens up an avenue for us to make pathway-based products, such as knock-out rats, cell lines or stem cells."
Researchers from the NHLBI and Boston University will publish the data from the study to make them accessible to other scientists.

"We believe this research will accelerate the development of new diagnostics and treatments for common life-threatening conditions," says Dr. Karen Antman, dean of Boston University's School of Medicine. "Our faculty takes great pride in being part of this exciting research, which may improve the lives of millions of people globally for the better."

A study funded in part by the NHLBI and published in the Aug. 5 issue of Nature scanned the genomes of more than 100,000 people from all over the world and found 95 genetic variants that contribute to changes in blood cholesterol and triglyceride levels in women and men of many ethnic backgrounds. Of the genetic variants, 59 had not been known and thus provide new clues for developing effective medicines to combat heart disease.

"The NHLBI is a leader in supporting long-term studies, including the decades-long Framingham Heart Study, that carefully track the health outcomes of large groups of people and generations of families," said NHLBI Acting Director Dr. Susan B. Shurin in a statement. "This genome-wide association study successfully demonstrates how cutting-edge genomics research can be leveraged by our past and current research investment in population-based studies assessing long-term health and disease."

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