Research Project
10256541
PROJECT SUMMARY Significance: Pre-operative embolization (POE) of meningiomas is an established neuroendovascular procedure performed to reduce the extensive amount of blood loss that occurs during tumor resection. The current practice is significantly hampered because of efficacy and safety deficiencies of current embolic agents used off-label for this indication (none of which are designed specifically for POE). Polyvinyl alcohol particles are the most used embolic agent, but efficacy data raise concerns of their clinical benefit. Trufill and Onyx are liquid-based embolic alternatives but are fraught with limitations of their own. For example, Onyx contains toxic solvent that causes patient pain and discomfort while the technical risks associated with Trufill have negated its wide-spread adoption in the United States. Thus, there is a need for an easy-to-use, on-label embolic agent designed specifically for POE of meningiomas that provides safe and complete devascularization. Such an embolic would result in faster and safer surgical resection, representing a significant evolution in the treatment of meningioma patients. Approach: In this Direct to Phase II SBIR, Arsenal Medical will advance its shear-thinning biomaterial technology, a flow responsive embolic (FRE) agent, as a therapy for the POE of meningiomas. For POE to be effective, complete devascularization of the meningioma is desired, which is achieved by total occlusion of all distal vessels that supply the tumor. Our Phase I results have demonstrated that the FRE exhibits superior distal penetration compared to commercial liquid embolics, is biocompatible, and can be manually injected through a neurovascular microcatheter. The goal of this proposal is to advance the proof-of-concept formulation towards a product configuration that is ready for clinical testing via an early feasibility study (EFS), enabling an efficient path to commercialization. In Aim 1, we will finalize the delivery system and affirm the product?s usability with clinicians. Aim 2 will consist of selection of a commercially viable sterilization method, followed by confirmation of product shelf-life. Biocompatibility of the FRE will be confirmed via a pre-clinical study to determine the neurovascular response and safety (Aim 3) and ISO10993 biocompatibility testing through biological and chemical characterization assays (Aim 4). The proposed work provides a foundational data set that will be complemented with post-Phase II activities to advance towards commercialization. Innovation: The FRE biomaterial has adaptive properties enabling it to become a low viscosity fluid under high shear that penetrates and fills the distal vessels supplying the meningioma. As embolization progresses, flow and shear will continually decrease; in response, the FRE progressively increases in viscosity becoming a viscous paste for controlled injection. The result is complete casting and occlusion of the entire vasculature. Compared to other liquid embolics, the FRE is less susceptible to incomplete occlusion because its solidification mechanism occurs independent of its microenvironment. Onyx, for example, solidifies via a precipitation effect, forming a hard outer shell that can block vessel branch pathways preventing them from deep vessel embolization.
