Drug-Device Combination Could Help Treat Stroke

A novel therapeutic approach combines a temporary endovascular bypass (TEB) with clot-busting nanoparticles to restore blood flow to obstructed vessels.

Developed by researchers at the Wyss Institute for Biologically Inspired Engineering (Boston, MA, USA), the New England Center for Stroke Research (NECSTR; Worcester, MA, USA) and other institutions, the drug-device combination is designed to quickly re-vascularize a vessel obstructed by a blood clot. The process involves an intra-arterial stent used to open a TEB, restoring enough blood flow to trigger a shear-activated nanotherapeutic (SA-NT) agent to dissolve the blood clot.

The SA-NT agent is composed of an aggregate of biodegradable nanoparticles coated with recombinant tissue plasminogen activator (r-tPA). As blood flow increases at the TEB location, the shear force grows, and the SA-NT agent reacts to it by releasing the r-tPA-coated nanoparticles in the partially occluded blood vessels. Hemodynamic stress causes the r-tPA to concentrate at the occlusion site, binding to the clot and dissolving it, thus providing high recanalization rates while reducing vascular injury.

After the blood clot is fully dissolved, the stent is re-sheathed and harmlessly removed from the vessel. If during the process any clot fragments break off and travel away through the circulatory system, the SA-NT drug-coated nanoparticles will remain bound to them and continue to dissolve them locally wherever they go. In clinically relevant large animal studies, the TEB/SA-NT combination worked very efficiently, dissolving clots that fully occluded brain blood vessels of the same size found in humans. The study was published on October 22, 2015, in Stroke.

“What's progressive about this approach is that the temporary opening of a tiny hole in the clot, using a stent device that is already commonly used clinically, results in a local rise in mechanical forces that activate the nanotherapeutic to deploy the clot-busting drug precisely where it can best do its job,” said senior author Donald Ingber, MD, PhD, of the Wyss Institute for Biologically Inspired Engineering.

“This has been a great collaboration between experts in the field of treating stroke and experts in mechanobiology and bioengineering,” said co-first author Netanel Korin, PhD, former Wyss Technology development fellow and current assistant professor in biomedical engineering at the Israel Institute of Technology (Technion; Haifa, Israel). “We hope that one day it will have a positive impact on patients suffering from a range of medical crises resulting from blood clot occlusions.”

Related Links:
Wyss Institute for Biologically Inspired Engineering
New England Center for Stroke Research
Israel Institute of Technology