# Development of a new marine natural product for the treatment of cryptosporidiosis, an AIDS-defining disease

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $474,114

## Abstract

ABSTRACT
 There are no effective therapies to treat Cryptosporidium, a waterborne parasite that is now recognized
as significant cause of diarrheal disease worldwide and an important AIDS defining pathogen. In the process
of mining compounds produced by marine symbiotic bacteria for anti-parasitic activity, we identified a
compound, tartrolon E (trtE) that potently inhibits in vitro growth of Cryptosporidium parvum, as well as several
other apicomplexan parasites, without toxicity to their respective host cells. We further established that trtE is
highly effective at reducing Cryptosporidium infection in neonatal mice. In fact, trtE is 10-fold more effective in
vitro and 2-fold more effective in vivo against Cryptosporidium than the most effective compounds reported to
date, and the only compound to hold the promise of a broad spectrum anti-apicomplexan therapeutic. These
observations strongly encourage further exploration of the clinical potential of trtE for the treatment of
cryptosporidiosis. In the studies proposed here, we will test the hypothesis that trtE possesses the activity
necessary to be lead candidate therapeutic for the treatment of cryptosporidiosis by completion of the following
aims: Aim 1: To evaluate species specificity and life cycle stage specificity of trtE against
Cryptosporidium. TrtE will be tested against C. parvum field isolates and C. hominis and the activity of trtE
against oocysts, sporozoites, asexual and sexual stages will be determined. Aim 2: To optimize trtE dosing
regimens. Pharmacodynamics (A), pharmacokinetics (B) and bioavailability (C) studies will be conducted to
design optimal treatment strategies. Aim 3: To evaluate the efficacy of trtE against Cryptosporidium
infection in the setting of severe immunosuppression and in a ruminant model of cryptosporidiosis. A.
We will test trtE’s ability to inhibit and eliminate Cryptosporidium infection in NOD-SCID gamma mice. B.
Because mice do not manifest the symptoms of human disease, we will test the trtE’s ability to inhibit infection
and diarrheal illness in neonatal lambs. Aim 4: To optimize production of trtE from Teredinibacter
turnerae T7901: Like many natural products, trtE has a complex structure that renders synthesis challenging
and prohibitively expensive. The Natural Products Discovery Institute (NPDI), experts in the field of natural
product production, will be producing trtE for these studies using established protocols. During that process,
NPDI will apply their expertise in this area to increase production efficiency. These studies will provide data
essential to establish trtE as a lead candidate for an anti-Cryptosporidium therapeutic. Moreover, because this
compound is highly active against multiple parasites, these investigations will underpin future studies
evaluating this compound as a broad spectrum therapeutic for diseases caused by apicomplexan parasites,
but most critically for cryptosporidiosis, a neglected disease of world-wide significa...

## Key facts

- **NIH application ID:** 10076207
- **Project number:** 1R01AI154943-01
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** ROBERTA M O'CONNOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $474,114
- **Award type:** 1
- **Project period:** 2020-06-12 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10076207

## Citation

> US National Institutes of Health, RePORTER application 10076207, Development of a new marine natural product for the treatment of cryptosporidiosis, an AIDS-defining disease (1R01AI154943-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10076207. Licensed CC0.

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