# Smart CSF Delivery System for CNS Drug Therapy for Leptomeningeal Disease

> **NIH NIH R43** · ENCLEAR THERAPIES, INC. · 2024 · $295,851

## Abstract

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.

## Key facts

- **NIH application ID:** 10819360
- **Project number:** 1R43CA281429-01A1
- **Recipient organization:** ENCLEAR THERAPIES, INC.
- **Principal Investigator:** MARCIE A GLICKSMAN
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $295,851
- **Award type:** 1
- **Project period:** 2024-07-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10819360

## Citation

> US National Institutes of Health, RePORTER application 10819360, Smart CSF Delivery System for CNS Drug Therapy for Leptomeningeal Disease (1R43CA281429-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10819360. Licensed CC0.

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