image: Brigitta Brott, M.D., and Ho-Wook Jun, Ph.D.
Credit: UAB
BIRMINGHAM, Ala. – The University of Alabama at Birmingham startup company Endomimetics, LLC, has received a $2.8 million Small Business Innovation Research Phase II grant from National Institute of Neurological Disorders and Stroke.
Under the grant, Endomimetics co-founders Ho-Wook Jun, Ph.D., a professor in the UAB Department of Biomedical Engineering, and Brigitta Brott, M.D., a professor in the UAB Department of Medicine Division of Cardiovascular Disease, will collaborate with Ramanathan Kadirvel, Ph.D., a professor of neurosurgery and radiology at Mayo Clinic, and David Kallmes, M.D., a professor of radiology at Mayo Clinic, Rochester, Minnesota, to develop a BionanomatrixTM coating for flow diverters in the brain.
More than 3 percent of the United States population — or about 6 million people — have an intracranial aneurysm, a bulge or ballooning in the wall of a blood vessel in the brain. The most feared risk for these people is rupture of the aneurysm, with devastating consequences.
In the past 15 years, intraluminal flow diversion devices have been used successfully as aneurysm therapy. Recent case studies have demonstrated high rates of long-term aneurysm occlusion by the flow diverters; but the most serious concern, and a significant cause of death after neurointervention, is a thromboembolism, a clot that blocks a blood vessel.
Thus, all patients treated with flow diverter devices require long-term antiplatelet therapy — a minimum of three months post-procedure — to reduce the body’s ability to form blood clots. If aneurysm occlusion could be accelerated and thrombus formation minimized, this could shorten the need for antiplatelet therapy and decrease risks of embolisms and bleeding.
Recent studies strongly suggest that complete endothelialization of any occlusion device is essential for durable occlusion, but with standard flow diverter technology, this endothelialization is prolonged. The Small Business Innovation Research grant will support research to evaluate whether applying Endomimetics’ Bionanomatrix coating to flow diverters will accelerate post-implantation healing.
The Endomimetics Bionanomatrix provides a native endothelium-mimicking environment that enhances endothelialization through five synergistic elements. The Bionanomatrix material: 1) Recruits endothelial cells from adjacent tissues through sustained release of nitric oxide; 2) Promotes endothelial cell retention through its adhesive ligands for endothelial cells; 3) Reduces inflammatory responses, and inhibits platelet adhesion and aggregation, through release of nitric oxide; 4) Is completely formed from biocompatible peptide-based materials; and 5) Is formed in a self-assembly coating method through water evaporation that avoids using any organic solvents.
The Bionanomatrix approach is innovative because it targets key factors that improve durable aneurysm occlusion by flow diverters and promotes endothelialization on the flow diverter while reducing inflammatory responses and platelet adhesion, Jun says. This could support the millions of people who depend on flow diverters for healing after intercranial aneurysms.
“Our proposal is significant as it addresses a critical and unmet clinical need in brain aneurysm patients — aneurysm occlusion with inhibited thromboembolism,” said Joseph Garner, CEO of Endomimetics. “Successful completion of the proposed studies will prepare Endomimetics to seek approval from the United States Food and Drug Administration for clinical trials using Bionanomatrix-coated flow diverters.”
Garner says Endomimetics is in discussion with potential corporate partners to license the technology and add Bionanomatrix-coated flow diverters to their product lines.
At UAB, Medicine is a department in the Marnix E. Heersink School of Medicine, and Biomedical Engineering is a joint-department in the Heersink School of Medicine and the UAB School of Engineering.