# Modulating Blood-Brain Barrier Permeability by TRPV4 activation

> **NIH NIH R21** · UNIVERSITY OF TEXAS DALLAS · 2024 · $447,501

## Abstract

Summary
The long-term vision of this proposed research is to build the next generation of methods to put medicine into
the brain and solve the most challenging and impactful neurological diseases. We plan to achieve this by
addressing the blood-brain barrier (BBB), the most significant barrier to delivering medicine to the brain.
Specifically, we aim to achieve cell type-specific control of the BBB by installing magnetic “switches” that would
allow therapeutic molecules across this barrier (
MagnetoBBB). This idea is based on two of our recent studies.
First, we have found that increasing intracellular calcium levels can change the BBB permeability, defined as the
ability of drugs to cross from the blood to the brain, based on our related studies using lasers and nanoparticles
to overcome the BBB. Second, our recent work on Ferritin-iron Redistribution to Ion Channels (FeRIC) has shown
the ability to induce calcium signals by producing biochemical signals and is safe in several cell types. In this
proposed work, we aim to establish the feasibility of cell-type specific modulation of the BBB with FeRIC and
magnetic field for drug delivery into the brain. To achieve these goals, we propose two specific aims. First, we
will investigate and optimize the BBB control using a human brain microvascular endothelial cell line or in vitro.
The in vitro system allows us to optimize and express the FeRIC constructs on the microvascular cell line for
magnetic field stimulation. We will characterize the calcium and calcium-induced signals inside these cells. We
will further determine the BBB changes by measuring the electrical resistance across a cell monolayer consisting
of these cells and the ability of molecules to cross the monolayer. Second, we will study the ability of
MagnetoBBB to control BBB inside a rodent brain or in vivo. We will first deliver the FeRIC genes into the
microvascular endothelial cells using viral and nonviral methods. We will then investigate the magnetic field
strength and duration needed to change BBB permeability in live brains. Our proposed approach will offer several
significant advantages over existing technologies. First, MagnetoBBB offers a physiologically-like mechanism to
modulate endothelial calcium levels and BBB permeability. Second, it allows non-invasive and cell-type specific
modulation of BBB with tissue penetrating RF field. Third, MagnetoBBB uses broadly accessible technology
suitable for multiple drug dosages such as chemotherapy, as the inexpensive RF coil can be made portable and
easily accessible. Lastly, the magnetic BBB switch is compatible with various imaging methods such as MRI
imaging to monitor the BBB opening and brain function. This proposed exploratory R21 addresses the key
aspects for a longer-term effort in cell type-specific control of the BBB for brain therapeutics.

## Key facts

- **NIH application ID:** 10999286
- **Project number:** 1R21NS135529-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS DALLAS
- **Principal Investigator:** Chunlei Liu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $447,501
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10999286

## Citation

> US National Institutes of Health, RePORTER application 10999286, Modulating Blood-Brain Barrier Permeability by TRPV4 activation (1R21NS135529-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10999286. Licensed CC0.

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