Miniscule, carefully engineered particles can detect the very beginning stages of clogged arteries in animals, thanks in large part to research at Washington University School of Medicine in St. Louis. With a new five-year, $7.3 million grant, School of Medicine researchers will begin to translate this breakthrough into clinical advances.
Funded by the National Heart, Lung and Blood Institute, the grant will support a Biomedical Research Partnership between the School of Medicine and several commercial partners, including Kereos Inc, Philips Medical Systems, Bristol-Myers Squibb Medical Imaging and Dow Chemical. The grant is an advancement of the School of Medicine’s BioMed 21 initiatives, which focus in part on translational research and biomedical imaging.
“We’ve developed a way to take images of very early arterial plaques, before they’re detectable by any other means,” says principal investigator Samuel A. Wickline, M.D., professor of medicine and of biomedical engineering at the School of Medicine and a Washington University heart specialist at Barnes-Jewish Hospital. “With this grant we will bridge the gap between fundamental laboratory research and the development of new, investigational drugs.”
Wickline and co-investigator Gregory M. Lanza, M.D., Ph.D., associate professor of medicine and biomedical engineering, are cofounders of Kereos Inc.
Hardened or clogged arteries, a condition called atherosclerosis, result from the accumulation of fatty plaques on the interior walls of blood vessels. As a plaque begins to form, a crowd of small blood vessels, called capillaries, develops around the site. Wickline and his colleagues designed a way to take images of those young capillaries, thereby predicting locations that will soon fall prey to atherosclerosis.
Their technique uses specially engineered nanoparticles that serve as mailmen — researchers tell the extremely small particles exactly what kind of cell to find and give them a package to deliver when they arrive.
In a study published in 2003, Wickline’s team packed nanoparticles with two components: molecules that latch onto small, rapidly growing capillaries and an imaging agent called gadolinium, which shows up as a bright spot on a magnetic resonance image (MRI). Using rabbits, they found that arteries that were developing dangerous capillaries had gadolinium signals twice as bright as normal arteries.
The researchers have shown that this technique also can help distinguish between stable plaques and those that are about to break apart. Fragments of plaques are a common cause of heart attacks or strokes.
Now that their technique has been proven effective in animals, the researchers will use the new grant to develop imaging agents that can be used in humans. They also hope to design drugs that can be delivered on nanoparticles to prevent a future heart attack or stroke.
“Our ultimate goal is to change the usual course of atherosclerosis by using imaging techniques to determine who is likely to have a stroke or heart attack and then targeting drugs to the site of the very earliest stages of disease,” Wickline says.
Although this grant does not directly fund clinical trials, Wickline believes the team’s research will be ready to be tested on patients in the next two to three years. And, because tumors also require new populations of capillaries, the team believes these techniques also may help detect very early cancers at the beginning stages of tumor development.
Editor’s note: Samuel A. Wickline, M.D., is a co-founder of Kereos Inc and is a board member and equity holder.
Lanza GM, Yu X, Winter PM, Abendschein DR, Karukstis KK, Scott MJ, Chinen LK, Fuhrhop RW, Scherrer DE, Wickline SA. Targeted antiproliferative drug delivery to vascular smooth muscle cells with a magnetic resonance imaging nanoparticle contrast agent: implications for rational therapy of restenosis. Circulation, vol. 106, pp. 2842-2847, 2002.
Wickline SA, Lanza GM. Nanotechnology for molecular imaging and targeted therapy. Circulation, vol. 107, pp. 1092-1095, 2003.
Winter PM, Morawski AM, Caruthers SD, Fuhrhop RW, Zhang H, Williams TA, Allen JS, Lacy EK, Robertson JD, Lanza G, Wickline SA. Molecular imaging of angiogenesis in early-stage atherosclerosis with alpha-v-beta-3-integrin-targeted nanoparticles. Circulation, vol. 108, pp. 2270-2274, 2003.
Buxton DB, Lee SC, Wickline SA, Ferrari M. Recommendations of the National Heart, Lung and Blood Institute Nanotechnology Working Group. Circulation, vol. 108, pp. 2737-2742, 2003.
Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.