# Carbohydrate-based Therapy for Lung Disease

> **NIH NIH P01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $2,543,475

## Abstract

Project Summary
The goal of this application is to translate our discovery of an unsuspected mechanism of mucus pathology into
a mucolytic drug strategy that could benefit millions of patients with mucus-associated lung disease.
Specifically, we have discovered that mucus elasticity in CF results from neutrophil oxidant stress that cross-
links mucin polymers to stiffen the airway mucus gel. Because oxidative stress occurs in multiple situations
associated with inflammation and environmental exposures, we hypothesize that oxidative stress is a
ubiquitous and previously unsuspected cause of increases in mucus elasticity in disease. This provides
rationale for developing mucolytic drugs with wide clinical utility that can cleave disulfide bonds as a
mechanism of action. Our tPPG group has synthesized novel thiol-modified carbohydrate compounds (“thiol-
saccharides”) and shown them to have potent mucolytic activity in CF sputum. We have encouraging
preliminary data for their formulation as dry powders and reassuring data regarding their safety. We now
propose three projects supported by two cores to bring a thiol-saccharide to the clinic as a new treatment for
CF and other mucus-associated lung diseases. Project 1 will modify carbohydrate scaffolds to create a library
of synthetic mucolytic compounds, conduct lead optimization studies, and formulate thiol-saccharides for
delivery as dry powders. Project 2 will screen the mucolytic efficacy of thiol-saccharide library to aid in
identification of lead compounds and the preclinical candidate compound and will identify a sub-population of
asthmatics who may benefit from mucolytic treatment. Project 3 will progress the lead thiol-saccharides to a
preclinical candidate and then to the clinic as a novel mucolytic strategy for mucus pathology in cystic fibrosis.
Cores A and B will provide all three projects with support in areas of administration, finance, communication,
data management and integration and human subjects. Our proposal is timely and highly clinically relevant,
and it is supported by strong preliminary data and high promise for realizing our goal.
PHS 398/2590 (Rev. 06/09) Page Continuation Format Page

## Key facts

- **NIH application ID:** 9990836
- **Project number:** 5P01HL128191-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** John V Fahy
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,543,475
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990836

## Citation

> US National Institutes of Health, RePORTER application 9990836, Carbohydrate-based Therapy for Lung Disease (5P01HL128191-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9990836. Licensed CC0.

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