# Design and development of HDAC11-specific chemical inhibitors for disease treatments

> **NIH NIH R01** · GEORGE WASHINGTON UNIVERSITY · 2022 · $697,517

## Abstract

Project Summary
 This resubmission proposal aims to elucidate the role of a histone deacetylase, HDAC11, in diseases such
as multiple sclerosis (MS), and to establish HDAC11 inhibition as a potentially effective new treatment strategy
for diseases including MS. MS is a chronic, immune-mediated demyelinating disease of the central nervous
system. Like many autoimmune disorders, it presently has no known cure, and current drugs available for
managing this disease are only effective early on and are accompanied by many adverse effects. The disease
mechanism of MS remains unclear, and no effective targeted therapy is available for chronic progressive MS.
Our preliminary studies show that deletion of HDAC11 ameliorates clinical symptoms in a mouse model of MS.
In parallel, we discovered a novel HDAC11 enzymatic activity that is >10,000-fold more efficient than its
deacetylase activity. This novel activity allows us to begin to uncover physiologic substrates of HDAC11, which
in turn will help to uncover the biological mechanisms of HDAC11’s actions. One of the goals of this research is
to investigate how this newly discovered enzymatic activity underlies the immune-regulatory function of
HDAC11 in MS. Knowledge gained from these studies will help to further understand the disease mechanism
of MS and to develop better therapeutics. Because the discovery of a novel HDAC11 activity has enabled us to
develop, for the first time, HDAC11-specific inhibitors, the chief objective is to further improve these inhibitors
and test whether they can be used to treat diseases such as MS in our established mouse models. Our
multidisciplinary team has expertise in all aspects needed to make this project successful. Overall, the
proposed studies in this application will not only yield a better understanding of HDAC11’s function in health
and diseases, but may also result in a first prototype targeted therapy for the treatment of chronic progressive
MS, and possibly other diseases as well.

## Key facts

- **NIH application ID:** 10360661
- **Project number:** 5R01AI153110-02
- **Recipient organization:** GEORGE WASHINGTON UNIVERSITY
- **Principal Investigator:** Hening Lin
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $697,517
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360661

## Citation

> US National Institutes of Health, RePORTER application 10360661, Design and development of HDAC11-specific chemical inhibitors for disease treatments (5R01AI153110-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10360661. Licensed CC0.

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