Synvista Collaboration Demonstrates in Preclinical Studies the Mechanism for Defective Cholesterol Transport in Patients wit... (ion for the defect in reverse cholestero...)

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Synvista Collaboration Demonstrates in Preclinical Studies the Mechanism for Defective Cholesterol Transport in Patients with Diabetes

Date:11/5/2007

ion for the defect in reverse cholesterol transport observed in many patients with diabetes mellitus (DM). Reverse cholesterol transport describes the process of moving cholesterol out of the atherosclerotic plaque and into HDL particles ("good cholesterol"). This process is thought to be the mechanism by which high levels of HDL protect patients from atherosclerotic disease. Dr. Asleh reports the presence of Haptoglobin-Hemoglobin (Hp-Hb) complexes in HDL particles and observes that Hp2-2-Hb complexes promote less efficient reverse cholesterol transport in DM, which can be reversed by antioxidants such as vitamin E. He proposes that strategies targeted to decrease oxidation of HDL in Hp2-2 patients may improve HDL function. Synvista has completed enrolling two cohorts of a three cohort Phase 2 clinical trial, evaluating among other endpoints, the impact of the Company's oxidized lipid metabolizing agent, ALT- 2074, on functional reverse cholesterol transport.

Radiolabeled Hp2-2-Hb complexes injected into mice and rats with and without diabetes demonstrated significantly longer half-life then radiolabeled Hp1-1-Hb complexes (e.g. 2-3 fold longer in non-DM animals, p=0001; and doubled in DM mice, p= 0.005). Coimmunoprecipitation studies showed that there is 10-fold more Hp2-2-Hb complex associated with HDL in diabetic mice than Hp1-1-Hb in non-DM mice. This was also shown in human sera where significantly more radioactive hemoglobin is associated with HDL particles in Hp2-2 individuals than Hp1-1 individuals. Reverse cholesterol transport, as measured by radiolabeled cholesterol efflux from pre-loaded macrophages, was significantly impaired (p=0.0001) by incubation with serum from Hp2-2 diabetic mice versus serum from non-DM Hp2-2 mice. This impairment was restored to normal levels when the mice received vitamin E.

About Synvista Therapeutics

Synvista Therapeutics is a biopharmaceutical company developing small molecule drugs to treat and prevent ca
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