# Proteostasis modulation in inherited blinding disorders

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $367,056

## Abstract

Title: Proteostasis modulation in inherited blinding disorders.
Abstract: Missense mutations of RPE or photoreceptor specific genes often cause inherited
blinding disorders. These mutated genes frequently yield protein products that are highly
unstable and prone to proteasomal degradation. We recently invented a novel drug discovery
strategy and identified a small molecule which can stabilize these mutated protein products. In
this project, we will test the therapeutic hypothesis that proteostasis modulation is a viable and
general therapeutic strategy for treating inherited blinding disorders caused by such protein
destabilizing missense mutations. Currently, no cures or treatments exist for the majority of
these blinding disorders. Toward the goal of fulfilling such unmet medical needs, we will study
the specificity (Aim1) and mechanism (Aim2) of the proteostasis modulation by our novel small
molecule. Moreover, we will prove the concept of the proteostasis modulation therapy using
mouse models of severe visual impairment and blindness (Aim3). This study will reveal novel
molecular pathways for stabilizing proteins whose loss of functions are associated with inherited
disorders. Such pathways will become attractive targets for various therapeutic molecules.

## Key facts

- **NIH application ID:** 10215855
- **Project number:** 7R01EY029680-03
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Yoshikazu Imanishi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $367,056
- **Award type:** 7
- **Project period:** 2019-02-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215855

## Citation

> US National Institutes of Health, RePORTER application 10215855, Proteostasis modulation in inherited blinding disorders (7R01EY029680-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10215855. Licensed CC0.

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