Collaboration to use proteomics to unravel mysteries of heart disease

September 03, 2002

DURHAM, N.C. -- Researchers from Duke University Medical Center; GeneProt, Inc., Geneva, Switzerland; and Novartis Pharma AG, Basel, Switzerland have launched a collaboration to identify how the proteins produced by heart disease patients differ from those of healthy people. Their research, which uses an industrial-scale approach to protein analysis and unusually large volumes of blood, could yield information that leads to new drugs or other treatments for coronary artery disease.

The researchers will compare blood samples from heart disease patients and normal people to detect subtle differences in the proteomes of the two groups. The proteome comprises the total number of proteins in an organism, much as a genome comprises its genes.

"This study is a new approach to unraveling the mysteries of the world's No. 1 health problem," said Duke's Chris Granger, a cardiologist at the Duke Clinical Research Institute and lead Duke investigator for the study.

"Although the sequencing of the human genome was heralded as one of science's greatest accomplishments, studies such as this one are essential for determining how the code of life produces the specific proteins that play a role in heart disease," Granger continued.

"This important project links the sophisticated capabilities of GeneProt in proteomic technologies, bioinformatics and protein synthesis to the exquisitely detailed patient phenotypes provided by Duke's unique Databank for Cardiovascular Diseases," said Sandy Williams, M.D., dean of the Duke University School of Medicine and vice chancellor for health affairs at Duke University Medical Center. "I believe this collaboration among Novartis, GeneProt and Duke University, under the leadership of Chris Granger, is a model for academic/industry relationships that will benefit our patients in the coming decade".

To assemble ideal comparison groups with and without coronary artery disease, the research team searched through the tens of thousands of patients entered in Duke's Databank for Cardiovascular Disease, -- the world's largest and longest-running cardiac catheterization-based database -- to select 241 patients who fulfilled specific criteria,. After matching such characteristics as gender, age and ethnicity, they narrowed the group further to 53 individuals, who matched closely with 53 healthy individuals. Then they collected blood from all of the participants and ended up with a total of six liters for each group.

"It is necessary to use large volumes in order to have sufficient quantities of those proteins present at very low concentration -- this involves pooling, which also serves to dilute normal differences with occur between individuals unrelated to the disease process," said Keith Rose, Ph.D., chief scientific officer for GeneProt.

GeneProt has completed its analysis of the smaller proteins and is now analyzing the larger proteins in the samples. Proteins that are present in one sample but not the other, or are present in widely differing amounts, are likely to be associated with the disease process and could be promising candidates for further investigation, according to Granger.

"This is the first time that in-depth proteomic analysis has been tackled on the scale of many liters of plasma, which is greater than 1,000 times more than is usually used," Rose said. "This allows identification of proteins in low concentration that may be novel and important factors in causing disease."

GeneProt then synthesizes the smaller interesting proteins, and Novartis will test them in further studies.

"We analyzed more than 25,000 fractions in our analysis of the small proteins and have delivered Novartis several releases of the protein database," Rose said. "Some interesting new proteins have already been synthesized, which validates our vision of an industrial-scale proteomics approach."

Granger has no financial interest in either GeneProt or Novartis.

Duke University Medical Center

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