SBIR-STTR Award

Neurovascular lesions, such as aneurysms and arteriovenous malformations (AVMs), are insidious and unpredictable. They often go unnoticed until the occurrence of a catastrophic hemorrhage or stroke. Approximately 350,000 patients experience hemorrhage annually, resulting in permanent loss of motor function, seizures, and death. Current neurosurgical therapies are risky and often ineffective at removing the life-threatening condition. The purpose of this venture is to provide an innovative biomaterial for treating neurovascular lesions from inside the vessel (endovascular embolization) in order to significantly increase therapeutic effectiveness while minimizing the surgical risks. Preliminary studies have identified calcium alginate (ALGEL) as a potentially non-adhesive, injectable, mechanically stable, and biocompatible material for effective occlusion of vascular lesions. A preliminary comprehensive in vitro aneurysm model has been developed, utilizing documented and tested neurovascular modeling techniques, to test ALGEL injectability and occlusion stability. Techniques learned will then be utilized to occlude chronic aneurysm models in swine. Lastly, a final round of chronic AVM models will also be occluded. The goal of the continued animal experiments is to utilize our knowledge in vivo modeling to complete 6-month chronic AVM and 1-month aneurysm occlusion studies for determining the long-term ALGEL stability and biocompatibility. The outcomes of the proposed project will be a solid foundation for the eventual development of safer and more effective treatments for life threatening aneurysms and high-grade AVMs. More generally, alginate embolization may also prove useful for minimally invasive vascular therapy of other vessel areas as well, such as blocking blood flow to tumors, stopping pelvic bleeding, treating uterine fibroids, and occluding other peripheral vessel damage and lesions.

Thesaurus Terms:
alginate, blood vessel disorder, embolism, technology /technique development cerebrovascular occlusion, disease /disorder model angiography, histochemistry /cytochemistry, swine

Neurovascular lesions are insidious and unpredictable. While there have been notable recent advances in minimally invasive access to these lesions using advanced micro-catheter systems, there is a paucity of equally high performing embolization materials that can be delivered through these catheters to effectively treat clinically challenging lesions. The overall goal of this project is to further develop a highly promising new hydrogel material for the endovascular treatment of aneurysms. This material, ALGEL-II(r), is an ultrapure alginate that is non-adhesive, injectable, mechanically stable, and biocompatible. Prior phases of this commercialization effort have resulted in successful pre-clinical studies and an IDE application to the FDA to begin clinical trials on ALGEL for embolization of arteriovenous malformations. The goal is to accomplish the next steps towards commercialization. Specific Aim 1 is to conduct materials testing of ALGEL-II to assess long-term stability and biocompatibility in small-neck aneurysms. This aim is directed at manufacturing clinical-grade ALGEL and completing FDA-standard long-term toxicity studies in mice and the required panel of genotoxicity studies. The final milestone of this aim is submission of an IDE application to the FDA for a Phase I clinical trial. Specific Aim 2 is to develop clinically appropriate techniques for using ALGEL to embolize wide-neck and bifurcation aneurysms. The studies will adopt a new animal model in dogs and compare the treatment and healing response to that previous found in swine. This project is based on a solid foundation of research and development in the clinical use of ALGEL for treating a wide range of neurovascular defects. The project team includes a core group of physicians, consultants, suppliers, and business alliances that has the technical, medical, and business expertise to make this project successful