Two four-year olds study digital proteomic signatures

Affomix and the PGx Centre to develop reagents that will enable the quantitative multiplexed profiling of strategic proteins predictive of drug efficacy and toxicity

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BRANFORD, Conn.—Affomix, founded in 2006 and now an aspiring leader in automated, high-throughput monoclonal antibody selection technology, will collaborate with the University of Montreal Pharmacogenomics Centre (PGx Centre), also launched in 2006, and the Montreal Heart Institute to consistently measure cardiovascular proteins, a key first step in identifying important biomarkers that will lead to a better understanding of atherosclerosis and how patients respond to various medications.

One of the PGx Centre's key strategies is to use diverse genomic and proteomic platforms to discover novel biomarkers that are predictive of drug efficacy and toxicity. Once validated, these biomarkers will be readily transferable to the clinical setting to provide improved personalized care to patients and guidance to health professionals based on appropriate selection and dosing of drugs. In a proof-of-principle test of its strategy, the center has identified a panel of proteins that it believes to be useful in predicting and evaluating response to novel anti-atherosclerotic agents in patients with cardiovascular disease. Affomix and the PGx Centre will work together to develop reagents that will enable the quantitative multiplexed profiling of these strategic proteins.

Affomix CEO Mike Sherman notes that genomics is useful for predicting disease, but less so for predicting response to treatment where proteomics has a "huge role to play from bench to bedside. We want to determine what disease the patient has, what stage it's in, and how it's responding to treatment," he says.

He notes that PCR is key to many genetic studies, but there is no equivalent technology for proteins.

"Protein concentration in cells is widely variable—up to 10 thousand times from protein to protein—which creates a problem with dynamic range. We have developed a set of reagents to detect proteins and measure them accurately," he says.

The process uses automated production and identification of antibodies and a recombinant process to measure them accurately. Sherman adds that the reagents can be used on any genomic sequencing machine.

"Our commercialization plan at Affomix has been to align the company's unique antibody-based capabilities with existing high-throughput, multi-analysis platforms, including next-generation sequencing technologies, thus providing quantitative proteome data to complement state-of-the-art genomic analyses," adds John Boyce, head of business development for Affomix. "We believe that the combination of our technological skills with the considerable clinical and informatics expertise of the Montreal Heart Institute could truly unlock the promise of pharmacogenomics."

"The field of pharmacogenomics has been hindered by its inability to determine complex proteomic signatures for prediction and determination of patient responses to treatment," says Dr. Michael Phillips, director of the PGx Centre. "Having the ability to consistently measure these cardiovascular proteins represents a key first step in identifying important biomarkers that will help us better understand atherosclerosis and how patients respond to certain medications."

He stresses that the goal is not just assay development, but to move quickly to the clinical setting. For example, the Affomix-PGx teams will look at HDL molecules to determine if there are changes with disease state and drug therapy.

"We know HDL is good," he says, "because its role is anti-inflammatory and anti-infective, but we need to know more about what happens to it in the clinical setting." He adds that lipid composition is another variable that will be studied.

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