# Latrunculin B as a new drug lead for the treatment of Acanthamoeba keratitis

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2021 · $236,875

## Abstract

PROJECT SUMMARY
Acanthamoeba keratitis (AK) can occur in healthy individuals wearing contact lenses and it is a painful blinding
infection of the cornea caused by a free-living ameba Acanthamoeba. Complications include chronic ocular
inflammation, corneal melting and scarring. Current treatment for AK relies on a combination of chlorhexidine,
propamidine isethionate, and polyhexamethylene biguanide. However, in 10% of cases recurrent infection
ensues, because of the difficulty in killing both trophozoites and double-walled cysts. Therefore, development
of efficient and safe drugs is a critical unmet need to avert blindness. Because AK is a rare disease, there is a
paucity of drug discovery efforts by the pharmaceutical industry and drug discovery for this infection largely
relies on academic research centers. To reduce the cost, time and risk associated with the development of
new AK therapies, we focused on the development of topical latrunculin B that completed Phase I/II safety,
tolerability and efficacy study in patients with ocular hypertension and glaucoma for the treatment of AK.
Marine natural product latrunculin B, which targets actin cytoskeleton of A. castellanii trophozoites and found
amebicidal in a phenotypic screen, laid the foundation for this proposal. Data related to this proposal show that
(1) latrunculin B is amebicidal against three clinical strains of A. castellanii, (2) a short treatment with low
concentration of latrunculin B led to depolymerization of actin filaments and subsequent disorganization of
acanthopodia in A. castellanii trophozoites, and (3) a novel image-based cysticidal assay developed by the PI
could be used to investigate the cysticidal effect of latrunculin B. Based on these data, we propose to 1) test
latrunculin B, against trophozoites and cysts of multiple genotypes of Acanthamoeba, 2) conduct tolerability
and pharmacokinetic-pharmacodynamic studies of topically administered latrunculin B for AK, and 3) test in
vivo efficacy of topical latrunculin B in an animal model of AK caused by Acanthamoeba of two different
genotypes. This study is a necessary step toward obtaining orphan drug designation of topically administered
latrunculin B for the treatment of AK. Given a deficit of the validated drug targets in Acanthamoeba, this study
will also enhance the development of novel targeted treatment option for AK. The results obtained in this work
may be expanded to other free-living amebae. To successfully achieve the proposal goals, we rely on our
collaboration that combines the unique expertise of Dr. Debnath (PI) in Acanthamoeba parasite biology and Dr.
Afshari in ophthalmology (Co-Investigator). Drs. Debnath and Afshari’s expertise and experience has potential
to elevate our drug discovery platform to a translational level.

## Key facts

- **NIH application ID:** 10192287
- **Project number:** 1R21EY032601-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Anjan Debnath
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $236,875
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192287

## Citation

> US National Institutes of Health, RePORTER application 10192287, Latrunculin B as a new drug lead for the treatment of Acanthamoeba keratitis (1R21EY032601-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10192287. Licensed CC0.

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