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Columns : May 1, 2008 ( )
Targeting Diabetes-Related Heart Disease
Synvista Is Developing a Molecular Diagnostic and Small Molecules for At-Risk Individuals!--h2>
In 2004, oncologist Noah Berkowitz, M.D., Ph.D., founded HaptoGuard with a focus on developing therapies for select patients with diabetes, namely those at high risk for cardiovascular complications identified by a specialized laboratory test. He was inspired by the success of cancer drugs like Herceptin that target tumors expressing a specific gene.
Three years later, HaptoGuard merged with Alteon, a 15-year-old company with drug candidates that attack advanced glycation end-products (AGEs). AGEs’ contribute to complications of diabetes, such as cardiovascular disease (CVD) and renal failure.
Dr. Berkowitz is now president and CEO of the new company called Synvista Therapeutics. The company’s focus is on novel products to control the formation of oxidized lipids and AGEs in diabetes and its underlying complications.
Glutathione Peroxidase Mimic
Synvista has two compounds in clinical trials ALT-2074 and alagebrium. ALT-2074 is a selenium-containing, small molecule drug that mimics glutathione peroxidase, a powerful antioxidant that reduces oxidized lipids.
Technology from the former HaptoGuard will be used to identify patients with diabetes who are at increased risk for CVD and who could benefit most from ALT-2074 or other treatments. The diagnostic test is based on haptoglobin, a protein that binds free hemoglobin in blood and acts as an antioxidant and antiatherosclerotic agent.
The company’s other drug candidate, alagebrium, was originally developed by Alteon researchers. Alagebrium breaks down AGEs, which crosslink proteins in tissues, leading to structural changes and deterioration that cause diastolic heart failure (DHF) and kidney failure. When proteins in the heart or other organs become crosslinked, they stiffen and cannot function properly. By breaking down crosslinks, alagebrium restores function to affected organs. “Alagebrium was picked up in a screen for chemicals that can interfere with the crosslinking process,” says Dr. Berkowitz.
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