# Repositioning of Clinically Approved Drugs toward the Prevention and Risk Evaluation of Early Cataract Progression

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2021 · $658,609

## Abstract

ABSTRACT
Age-related cataract is a universal, slowly progressive, insidious blinding disease that affects 20
million Americans above the age of 65 years. Yet, it is unclear why cataract progresses faster in
some vs other individuals who are seemingly protected and cataract free at an advanced age.
The existence of differential progression rates of lens opacification among individuals implies the
existence of protective as well as deleterious factors that are as yet poorly understood. We
hypothesize that there are, among today’s clinically approved drugs, candidate drugs that
have anti-cataract properties, and therefore could be developed as such, while others may
have cataract promoting properties unbeknownst to patients and the medical community.
To test this hypothesis, we propose to combine two innovative and complementary approaches,
i.e. a computational approach to simultaneously identify, among clinically approved drugs,
potentially anti- and pro-cataractogenic compounds, with an experimental approach geared at
simultaneously identifying drugs that prevent or worsen in vitro generated oxidative stress and
lens crystallin destabilization. Candidate drugs emerging from this dual approach will be tested in
mouse models of age-related cataract.
 Using a multi-PI strategy consisting of a team of experts in computational drug
repositioning, and a team of experts in high throughput screening of small molecules, animal
models of age-related cataract, in oxidative stress and protein aggregation, we propose four
focused and achievable goals over a four year period: Aim 1: Development of novel data-driven
computational algorithms to identify repositioned anti-cataract drugs and cataract risk promoting
drugs from all FDA-approved drugs. Aim 2: Testing of 2650 FDA approved clinical drugs from
the Microsource Spectrum library for their efficacy or deleterious properties on protein
aggregation/denaturation in three in vitro stress model systems, i.e. oxidative metabolic damage
to gamma and beta crystallins, UV irradiation and whole lens in vitro incubation stress. Aim 3:
Test the top candidate drugs emerging from the above in silico and experimental search for their
potential therapeutic or deleterious activity on cataract progression in two mouse models of
cataract, i.e. the LEGSKO/Gclm (Double knockout) DKO mouse and the alphaB crystallin R120G
mutant knock-in mouse. Aim 4: Develop a comprehensive knowledge base and make all the data
publicly available via interactive web application. The successful execution of this innovative
program is expected to have a transformative impact in the cataract field by potentially
repositioning known drugs toward both early cataract prevention as well cataract progression risk
assessment.

## Key facts

- **NIH application ID:** 10164795
- **Project number:** 5R01EY029297-03
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** VINCENT M MONNIER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $658,609
- **Award type:** 5
- **Project period:** 2019-06-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10164795

## Citation

> US National Institutes of Health, RePORTER application 10164795, Repositioning of Clinically Approved Drugs toward the Prevention and Risk Evaluation of Early Cataract Progression (5R01EY029297-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10164795. Licensed CC0.

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