Smart CSF Delivery System for CNS Drug Therapy for Leptomeningeal Disease

Project Summary / Abstract Cancer cells that enter the brain are difficult to treat with standard intravenous administration of chemotherapies due to the blood-brain barrier. Intrathecal administration of Methotrexate, Topotecan, and other chemotherapies have been used in the past to overcome the brain-blood

barrier (BBB) and enhance the dose delivered to the subarachnoid space, though results in poor tissue distribution and tissue penetration is often not that deep into the tissue. To address this, EnClear created a platform technology to access the cerebrospinal fluid (CSF) and deliver therapeutic agents controlling the circulating dosed CSF between the lumbar

subarachnoid space and the lateral cerebral ventricles. This enhanced delivery is intended to control dose delivery throughout the cerebrospinal space to target areas of interest. In contrast, passive intrathecal delivery relies on the natural circulation of CSF to deliver the chemotherapy throughout the subarachnoid space. With the rapid turnover of CSF (4-5 times in humans), the

drug is cleared quickly with passive diffusion in the CSF. The purpose of this Phase 1 grant is to demonstrate the safety and feasibility of optimal delivery of Topotecan in a large animal model. In pursuing the aims of this grant, we will 1) Further develop and optimize a preclinical CSF extracorporeal flow system for subarachnoid chemotherapy delivery; 2) Test the preclinical

system in a bench-top flow loop and; and 3) Demonstrate the feasibility and safety with our sensor array of the EnClear preclinical delivery system in a minipig glioma tumor model with Topotecan treatment. In Phase 2, we will develop the final device, bring it through design verification, expand the animal efficacy cancer model, perform a GLP animal safety study and

prepare the necessary testing for an Investigational Device Exemption application to FDA to perform a first-in-human study.