Stroke Treatment Uses Blood Flow to Trigger tPA Release

By: Hannah Stuart
Wednesday, June 1, 2016

Researchers are developing a means to quickly dissolve blood clots using a drug-and-device combination that also reduces vascular injury.

The technique for treating stroke is the work of scientists at the University of Massachusetts’ New England Center for Stroke Research and Harvard’s Wyss Institute. The technique uses nanoparticles coated with clot-dissolving tissue plasminogen activator (tPA) in conjunction with a stent device commonly used in cardiac blockages to quickly restore blood flow in the brain. The stent creates a narrow opening through the clot to create shear force of blood flow, which activates the nanoparticles to release tPA at the site of the blockage.

“The idea is that [the nanoparticles] travel around like a platelet as an aggregate, and they’re coated with tPA,” says Donald Ingber, MD, PhD, Founding Director at Wyss Institute for Biologically Inspired Engineering and Judah Folkman Professor of Vascular Biology at Harvard Medical School. “When they see high shear stress, they break up ... and bind fibrin in the clot, and so we would concentrate the drug right at the site where the clot was formed.”

The study, whose findings were published recently in the journal Stroke, was conducted in clinically relevant large animals and demonstrated that the therapy is efficient in dissolving clots that are fully occluding brain blood vessels.

Refining Previous Techniques

The technique enhances safety as well.

“You don’t take the stent out — you don’t drag it out, you re-sheath it into a micro-catheter,” says Matthew Gounis, PhD, Associate Professor of Radiology at the University of Massachusetts Medical School and Director of the New England Center for Stroke Research. “You can safely pull the whole system out after the clot is dissolved because of this nanoparticle delivery system.”

Researchers found injury to the vessel was significantly less using the combined approach than when a stent is pulled out during a stent-retriever thrombectomy.

“When you pull out the clot with these stentrievers, not only do you get local injuries and secondary inflammation, but you also break down the clot,” says Ajay Wakhloo, MD, PhD, Fellow of the American Heart Association, Director of Neurointervention and Imaging, and Professor of Neurology, Neurosurgery and Radiology at the University of Massachusetts Medical School. “What you see in about 10 to 15 percent of the patients is smaller particles of clot migrating into the smaller vessels, and that may create further injury to the brain tissue.”

Dr. Gounis stresses that stent-retriever thrombectomy is a very effective technique, calling it the single greatest advance in stroke treatment, but he notes that research is moving ever forward.

“What we have learned from these data [is] that it’s very important to rapidly get complete reperfusion of the ischemic brain,” he says. “In our research, what we showed was a very high rate of obtaining complete angiographic reperfusion when the treatment was tailored appropriately — using roughly the equivalent of 20 milligrams of free tPA in combination with the stent.”