# Enabling Intranasal Therapies for Brain Invading Pathogens

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2024 · $241,949

## Abstract

The blood-brain barrier (BBB) plays the role of maintaining brain homeostasis and preventing foreign 
invaders from infiltrating the brain tissue from the blood; however, an alternative pathway exists for 
opportunistic pathogens to enter the brain and cause severe damage. Infiltrating either through the olfactory 
or trigeminal nerves (in the nose), these pathogens, whether bacterial, viral, fungal, or parasitic, bypass the 
BBB and cause devastating symptoms. Like brain tumors, these neural infiltrating pathogens are free to grow 
with the protection afforded them by the BBB, which prevents the passage of greater than 98% of small 
molecule drugs. Because of the difficulty associated with treatment, pathogenic infections can lead to 
meningitis, with insufficient treatments available, demonstrated by mortality rates that range from ~10% to 
98%, depending on the etiology. Although these pathogens vary in their etiology and pathology, many of 
them are linked by enolase, an enzyme that plays a role in plasminogen binding and glucose metabolism, 
which seems to enable their infiltration. The Larsen Lab is a leading expert in the development of 
treatments for diseases of the central nervous system using polymer-based nanoparticles to 
encapsulate and deliver drugs across the BBB. We will leverage this expertise towards the treatment of 
brain-invading pathogens. Learning from these opportunistic pathogens, we will encapsulate enolase 
inhibitors in polymer-based nanoparticles called polymersomes and deliver them via intranasal 
administration. In this proposal, we specifically focus on brain-eating amoeba, or Naegleria fowleri, as our 
first model to provide proof of concept for our approach due to its extremely high mortality rate. We plan to 
leverage discoveries for treatments of other pathogens involving enolase.

## Key facts

- **NIH application ID:** 11096412
- **Project number:** 5P20GM146584-03
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Jessica Marie Larsen
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $241,949
- **Award type:** 5
- **Project period:** 2024-06-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11096412

## Citation

> US National Institutes of Health, RePORTER application 11096412, Enabling Intranasal Therapies for Brain Invading Pathogens (5P20GM146584-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11096412. Licensed CC0.

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