A protein-based drug being developed at ASU could help
prevent failure of coronary bypass surgery.
In coronary bypass surgery, veins are removed from the legs and used to
bypass blocked arteries around the heart. One of the primary reasons the
procedure fails is vasospasm, the clenching of the transplanted vein, when
it is removed from the body. Bleeding in the brain from a ruptured aneurysm
can also cause severe spasm of nearby blood vessels, which leads to stroke.
 Nitric oxide gas causes the relaxation of smooth muscle, which is found in
blood vessels and other organs, by triggering a complex signaling pathway in
the cell. Colleen Brophy, research professor of bioengineering and director
of the Center for Protein and Peptide Pharmaceuticals in the Arizona
Biodesign Institute, found that an enzyme activates the last protein in this
pathway, called HSP20, by adding a phosphate group to it. Thus, Brophy and
colleagues are creating a phosphorylated mimetic of HSP20 as a potential
drug to prevent vasospasm.
Most drugs are small molecules that can be made chemically. A protein is
huge in comparison, difficult to get inside a cell, and may require a
biological system for production. Yet, a protein-based drug is more
efficient and highly targeted. “You’ve got all those signaling pathways,
but, boom, you bypass them by putting in a mimetic of the protein that’s the
effector molecule,” Brophy said.
To create the HSP20 mimetics, Brophy’s lab has used computer models to look
at potential improvements to the protein. Promising mimetics are made in the
laboratory, then tested if they cause relaxation in strips of blood vessel,
then laboratory animals. The next step is to take a HSP20 mimetic into stage
one clinical trials so that its efficacy and safety in humans can be tested.
“I’m interested in approaching science from a bedside to bench and back to
bedside approach,” Brophy said. “We hope this group to be very applied in
terms of looking at clinically relevant problems for which there’s an unmet
need, then developing experimental approaches to solving these problems, and
then, based on experimental discoveries, engineer molecules that can be used
to treat human disease. And bring it back to the bedside to treat patients.”
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