Synvista Therapeutics (Montvale, New Jersey) reported favorable findings from a study that indicated its proporietary monoclonal enzyme immunoassay can help in predicting cardiovascular risk in patients with diabetes.

The findings were presented at the Cardiovascular Biomarkers and Surrogate Endpoints Symposium in Bethesda, Maryland, last week.

In the study, investigators developed an ELISA (enzyme-linked immunosorbent assay) using a monoclonal antibody that differentiates between the three haptoglobin pheno/genotypes. Blood samples from diabetic patients with known haptoglobin pheno/genotypes were tested using Synvista's proprietary methodology.

Results demonstrated 99.5% accuracy in determining each of the three haptoglobin types (48/48 Hp 1-1, 49/49 Hp2-1 and 90/91 Hp-2-2) with a =98% sensitivity and specificity for each phenotype.

"The test has been under development throughout the past year," Noah Berkowitz, president/CEO of Synvista, told Diagnostics & Imaging Week. "This study shows the utility of our proprietary technology to diagnose Hp2-2 diabetes, a disease affecting almost 7 million people in the U.S.

He added, "We believe that the ease of use of our haptoglobin diagnostic technology and rapid results bode well for its acceptance as an important tool in the treatment of cardiovascular disease in diabetic patients. In addition, we believe that the development of genetic markers like those identified by our test will continue to pave the way toward a personalized medicine model that will benefit a wider variety of patients in a more direct and reliably predictive manner."

The company said the ELISA assay was developed using a monoclonal antibody that can differentiate between each of the three Hp phenotypes. Serum samples from diabetics of known phenotype/genotype were diluted 1:10 and incubated in microtiter strips coated with an anti-human Haptoglobin monoclonal antibody for 30 minutes. The strips are washed and incubated for 30 minutes with monoclonal anti-human Haptoglobin conjugated to horseradish peroxidase.

The strips are washed and developed with TMB, a peroxidase substrate, for 15 minutes. The absorbance is read on a plate reader at 450 nm. Positive controls for each phenotype also are run to ensure the assay is performing properly. Cutoffs for each phenotype are set for each lot of strips and conjugate.

Haptoglobin, a core component of the immunoassay, is found in humans and comes in the form of three different proteins that arise from one of three gene combinations in the population, Hp 1-1 (16%), Hp2-2 (36%) and Hp1-2 (48%). For a variety of reasons, Hp2-2 is more effective than Hp1-1 at preventing hemoglobin-induced oxidation in the bloodstream and blood vessel wall.

As a result, scientists have determined that the rate of heart disease is five times higher in Hp2-2 diabetes than in Hp1-1 diabetes. Hp2-2 diabetes also has higher rates of myocardial infarction and re-vascularization within one year of angioplasty, and of heart failure and death following a heart attack.

Prospective clinical trials have demonstrated that the rate of heart attack in Hp2-2 diabetes can be decreased by the administration of natural vitamin E.

The company said that this combination of testing and treatment exemplifies pharmacogenomics, the targeting of a particular drug on the basis of genetic testing.

"So the test can determine which patients can benefit from taking vitamin E," Berkowitz said. "The feedback from the medical community is beginning to swell. We believe there's an opportunity worldwide to treat and reduce diabetes."

The company is working on a plethora of other applications, including alagebrium, a proposed breaker of advanced glycation endproducts for the treatment of systolic and diastolic heart failure. Alagebrium has demonstrated relevant clinical activity in two Phase II clinical trials in heart failure, as well as in animal models of heart failure and nephropathy, among others.

Alagebrium has been tested in nearly 1,000 patients in multiple Phase I and Phase II clinical trials, allowing Synvista to assemble a sizeable human safety database.

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