Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

The video associated with this looks great. When do we get this in real life?  What is your doctor and hospital doing to get this validated? What about your stroke association doing ANYTHING AT ALL?
Video here:
https://www.facebook.com/ScienceNaturePage/videos/778434595622134/

Press release here:
http://wyss.harvard.edu/viewpressrelease/224/drugdevice-combination-opens-potential-new-path-to-treat-stroke

 Research article here:
Shear-Activated Nanoparticle Aggregates Combined With Temporary Endovascular Bypass to Treat Large Vessel Occlusion

1. Miklos G. Marosfoi, MD*,
2. Netanel Korin, PhD*,
3. Matthew J. Gounis, PhD*,
4. Oktay Uzun, PhD,
5. Srinivasan Vedantham, PhD,
6. Erin T. Langan, BS,
7. Anne-Laure Papa, PhD,
8. Olivia W. Brooks,
9. Chris Johnson, BS,
10. Ajit S. Puri, MD,
11. Deen Bhatta, MS,
12. Mathumai Kanapathipillai, PhD,
13. Ben R. Bronstein, MD,
14. Ju-Yu Chueh, PhD,
15. Donald E. Ingber, MD, PhD† and
16. Ajay K. Wakhloo, MD, PhD†

+ Author Affiliations

1. From the New England Center for Stroke Research, Department of Radiology, University of Massachusetts, Worcester (M.G.M., M.J.G., S.V., E.T.L., O.W.B., A.S.P., J.-Y.C., A.K.W.); Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA (N.K., O.U., A.-L.P., C.J., D.B., M.K., B.R.B., D.E.I.); Department of Biomedical Engineering, Technion, Israel (N.K.); Vascular Biology Program, Boston Children’s Hospital and Harvard University, Boston, MA (D.E.I.); and Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA (D.E.I.).

1. Correspondence to Donald E. Ingber, MD, PhD, Wyss Institute at Harvard, CLSB5, 3 Blackfan Circle, Boston, MA 02115. E-mail don.ingber@wyss.harvard.edu

1. ↵* Drs Marosfoi, Korin, and Gounis contributed equally.
2. ↵† Drs Ingber and Wakhloo are joint senior authors.

Abstract

Background and Purpose—The goal of this study is to combine temporary endovascular bypass (TEB) with a novel shear-activated nanotherapeutic (SA-NT) that releases recombinant tissue-type plasminogen activator (r-tPA) when exposed to high levels of hemodynamic stress and to determine if this approach can be used to concentrate r-tPA at occlusion sites based on high shear stresses created by stent placement.

Methods—A rabbit model of carotid vessel occlusion was used to test the hypothesis that SA-NT treatment coupled with TEB provides high recanalization rates while reducing vascular injury. We evaluated angiographic recanalization with TEB alone, intra-arterial delivery of soluble r-tPA alone, or TEB combined with 2 doses of intra-arterial infusion of either the SA-NT or soluble r-tPA. Vascular injury was compared against stent-retriever thrombectomy.

Results—Shear-targeted delivery of r-tPA using the SA-NT resulted in the highest rate of complete recanalization when compared with controls (P=0.0011). SA-NT (20 mg) had a higher likelihood of obtaining complete recanalization as compared with TEB alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), intra-arterial r-tPA alone (odds ratio 65.019, 95% confidence interval 1.77, >1000; P=0.0231), or TEB with soluble r-tPA (2 mg; odds ratio 18.78, 95% confidence interval 1.28, 275.05; P=0.0322). Histological analysis showed circumferential loss of endothelium restricted to the area where the TEB was deployed; however, there was significantly less vascular injury using a TEB as compared with stent-retriever procedure (odds ratio 12.97, 95% confidence interval 8.01, 21.02; P<0.0001).

Conclusions—A novel intra-arterial, nanoparticle-based thrombolytic therapy combined with TEB achieves high rates of complete recanalization. Moreover, this approach reduces vascular trauma as compared with stent-retriever thrombectomy.