MAGNETIC (MRI-Assisted Guidance via NeuroInterventional Targeted Imaging Catheters) - PROJECT SUMMARY Intra-arterial (IA) drug delivery offers a promising approach for treating neurological diseases by delivering therapeutic agents directly to the brain. However, traditional methods face significant challenges, including procedural variability and the inability to confirm blood-brain barrier (BBB) permeability in real time. These challenges are further compounded by unique vascular anatomies and cerebral hemodynamics[1,2]. We are developing PassiveCath, an innovative microcatheter device designed for enhanced visibility and drug delivery to the central nervous system (CNS). PassiveCath is equipped with passive tracking markers, allowing for real-time MRI navigation, thereby eliminating the need for fluoroscopy and exposure to ionizing radiation. PassiveCath aims to significantly improve the safety and efficacy of IA drug delivery, particularly when combined with established techniques like mannitol-mediated osmotic blood-brain barrier opening (OBBBO). This method has shown potential in treating a range of neurological conditions, including primary and metastatic brain tumors, neurodegenerative disorders, and inherited neurodegenerative metabolic disorders. By facilitating the precise administration of drugs, such as viral vectors, antivirals, and large-molecule therapies, PassiveCath enhances treatment efficacy by minimizing systemic toxicity with super-selective therapy delivery. The core innovation of PassiveCath lies in its ability to provide real-time feedback on catheter placement, drug distribution, and BBB status during OBBBO procedures. This functionality is crucial for optimizing therapeutic efficacy and ensuring patient safety. Unlike conventional catheters that rely on X-ray fluoroscopic guidance, PassiveCath's MRI visibility allows for more accurate targeting and monitoring, potentially leading to better outcomes and a broader adoption of advanced image-guided therapeutic techniques. In this Phase I STTR proposal, we aim to validate PassiveCath in vivo, leveraging its innovative design to improve the precision and safety of IA drug delivery following OBBBO. PassiveCath will function as part of a larger MR-safe device and image guidance ecosystem developed in a completed NIH R01 project (R01EB012031), focused on guide catheter designs with neurointerventional device leaders in the industry. PassiveCath will be placed coaxially through the lumens of MR-safe guide catheters to constitute the first fully MR-compatible and visible, clinical-grade endovascular CNS infusion system. Our current objectives include demonstrating PassiveCath’s MRI visibility, safety and biocompatibility, and impact on MR-guided drug delivery in animal models. Proof-of-concept has been established through phantom models and in vivo navigation studies. We will conduct further in vivo testing in established swine models to statistically validate the efficacy, safety, and reduction of procedure-related toxicities associated with PassiveCath. Successful completion of these specific aims will facilitate FDA 510(k) approval, positioning PassiveCath as a groundbreaking, low-cost, minimally invasive solution for enhancing IA drug delivery of neurological therapies previously limited by availability of safe and effective targeting methods[2]. Ultimately, PassiveCath has the potential to transform the current paradigm of IA drug delivery, not only in neuro-oncology but also in the broader field of neurology[3,4]. Its application could extend to other therapeutic areas where precise, image-guided drug delivery is critical, offering a versatile platform for various drug-disease combinations. This work will set the stage for Phase II studies, which will focus on clinical translation, paving the way for widespread clinical adoption and improved patient outcomes.
