# Targeting HDAC6 to Modulate Titin Stiffness for Dilated Cardiomyopathy Therapy

> **NIH NIH R43** · EIKONIZO THERAPEUTICS, INC. · 2020 · $300,000

## Abstract

PROJECT SUMMARY/ABSTRACT
Dilated cardiomyopathy (DCM) is associated with impaired systolic/pump function of the heart, which can lead
to heart failure and death. It is estimated that 1 in 250 adults in the U.S. have DCM, with ~40% of these cases
being attributed to genetic causes. A common characteristic of DCM is reduced stiffness of titin. Titin is a
molecular spring that provides passive tension to the heart by functioning within contractile units known as
myofibrils. It is believed that re-establishing titin spring function (i.e. stiffening titin) in DCM patients could provide
an innovative, disease-modifying approach to treat cardiomyopathy. Unpublished findings from our collaborator,
Dr. McKinsey, reveal a remarkable ability of the cytoplasmic protein, histone deacetylase 6 (HDAC6), to control
the stiffness of titin. The long-term objective of the proposed work is to develop an HDAC6-selective small
molecule inhibitor as a ‘titin stiffener’ to improve systolic function and treat DCM in humans. This is in-line with
the mission of the NHLBI, which includes treatment of heart disease to enhance the health of individuals so they
can live longer and more fulfilling lives. One specific aim is to rank-order novel HDAC6 inhibitors (discovered by
Eikonizo Therapeutics) for their ability to increase titin stiffness in cultured adult rat cardiomyocytes, and for their
ability to improve systolic cardiac function in a short-term mouse model of heart failure. In a second specific aim,
compounds that advance through these initial filters will be tested for efficacy in a rat model of DCM characterized
by severe titin softening. This rat model recapitulates many elements of RBM20 (RNA-binding motif protein 20,
a splicing factor that targets titin) cardiomyopathy, an aggressive and early onset genetic DCM in humans. This
drug discovery proposal has the potential to facilitate the development of transformative therapies to treat DCM
in humans.

## Key facts

- **NIH application ID:** 10080922
- **Project number:** 1R43HL154959-01
- **Recipient organization:** EIKONIZO THERAPEUTICS, INC.
- **Principal Investigator:** Frederick Albert Schroeder
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $300,000
- **Award type:** 1
- **Project period:** 2020-09-01 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10080922

## Citation

> US National Institutes of Health, RePORTER application 10080922, Targeting HDAC6 to Modulate Titin Stiffness for Dilated Cardiomyopathy Therapy (1R43HL154959-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10080922. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*