# Innovative natriuretic peptide-based therapy for hypertrophic cardiomyopathy

> **NIH NIH F32** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $80,746

## Abstract

Project Summary/Abstract
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder, affecting 1 in every 200-
500 individuals. Cardiac fibrosis in HCM is a key determinant of the risk of heart failure (HF), arrhythmia and
sudden cardiac death. Approximately 5% of patients with HCM progress to end-stage disease with systolic
dysfunction, for which cardiac transplantation is the only durable therapeutic option. There is no proven medical
therapy for HCM that modifies fibrosis, a key pathophysiologic process that leads to clinical decompensation and
adverse outcome. There is a critical unmet need for therapies targeting fibrosis in HCM. C-type natriuretic peptide
(CNP) is the most potent anti-fibrotic natriuretic peptide, and CNP has been shown to attenuate fibrosis in
disease other HCM. It is unknown if levels of CNP are altered in patients with HCM. Furthermore, it is unknown
if CNP-based therapy could be effective in HCM. We will attempt to address these questions with the present
project. First, we will compare levels of CNP in humans with HCM compared to healthy controls. These data will
provide critical information on the role of CNP in the development of fibrosis in HCM. Second, using a mouse
model of HCM, we will test if administering CNP-based peptides can prevent or reverse cardiac fibrosis. In
addition to focusing on CNP, we will also measure other key enzymes in CNP signaling. Neprilysin is the principle
mechanism for enzymatic degradation of CNP, and therefore inhibiting neprilysin may be an alternative strategy
to prevent fibrosis in HCM. Using a combination of clinical specimens and mouse models, this translational
project will lay the foundation for innovative CNP-based therapy in HCM and testing in humans. The development
of novel CNP-based therapeutics targeting fibrosis will also provide future inventive to apply this strategy to other
diseases such as dilated cardiomyopathy and arrhythmogenic cardiomyopathy. Overall, our translational
approach will identify the role of CNP in HCM, and determine if augmenting CNP is a viable therapeutic strategy
to prevent fibrosis in HCM.

## Key facts

- **NIH application ID:** 10537838
- **Project number:** 1F32HL165917-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** David William John Armstrong
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $80,746
- **Award type:** 1
- **Project period:** 2022-09-25 → 2024-08-24

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10537838

## Citation

> US National Institutes of Health, RePORTER application 10537838, Innovative natriuretic peptide-based therapy for hypertrophic cardiomyopathy (1F32HL165917-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10537838. Licensed CC0.

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