Breakthrough Diabetes Treatment

Researchers developing a drug that could stop, if not reverse, the progression of atherosclerosis – a buildup of fatty tissue in the veins that causes heart attacks and strokes.

Dr. David Clemmons has toiled in his University of North Carolina at Chapel Hill lab to develop a drug that could stop, if not reverse, the progression of atherosclerosis – had immersed himself in the intricate interactions of the smooth muscle tissue that comprise vascular walls.

If it’s effective in humans and doesn’t produce toxic side effects, the drug could have an enormous effect on how doctors treat diabetics who have exhausted other forms of treatment.

Current treatments for atherosclerosis, including statins, can slow the development of fatty lesions in the veins and help prevent them from forming. But nothing to date has been proven to stop or reverse the condition once it begins. Clemmons’ research could introduce an entirely new class of drugs to the market while providing hope for diabetics at risk of having a massive heart attack or stroke.

"The potential impact of this is huge, if it makes it through all of the hurdles," says Clemmons, chief of the Division of Endocrinology and Metabolism at the UNC School of Medicine.

Clemmons’ goal is to have the drug – which for now is being called the Cysteine Loop Monoclonal Antibody, or C-loop mAb, for short – in pre-clinical trials in pigs by March and in human trials by late 2008.

According to a UNC market analysis for the drug, based on data from the Centers for Disease Control and Prevention, 1.2 million diabetics in 2004 were diagnosed with atherosclerosis severe enough to warrant them getting a stent placement. Of those, 57 percent, or 456,000 people, had recurring lesions severe enough that they required a new stent a year later. That’s the population Clemmons’ drug could help.

Clemmons took what he calls a "fairly major risk" in 1998 – the same year he brought on fellow researcher Laura Maile – when he decided to narrow the scope of his work and refocus his lab on the development of a protein-based treatment for atherosclerosis.

In 2003, they hit their mark. Adding excessive amounts of glucose – a hallmark of diabetes – to their experiment, they found a protein therapy that blocked a cellular interaction that allows the deadly lesions to form in the veins. The strategy works by inhibiting a protein that, when active, binds fatty tissue cells to the wall of the vein.

What sets Clemmons’ research apart is his particular protein target – the alpha V beta 3 integrin, a protein found for the most part only in the cells that make up the smooth muscle tissue of veins. Other attempts at developing a treatment have been aimed at more common proteins. They were discovered to be toxic. Existing treatments such as statins don’t do much long-term good.

"The other drug classes that have been tried … if given in high doses can slow the rate of progression," Clemmons says. "But again, it’s a small effect. We’re looking for something that’s much, much bigger than that."

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