# Prospective Development of a Multimodal Biomaker Platform for Predictive Risk Stratification of Cardiac Disease in Duchenne Muscular Dystrophy

> **NIH FDA R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $577,922

## Abstract

PROJECT SUMMARY/ABSTRACT
Duchenne muscular dystrophy (DMD) is a rare and devastating disease with no cure affecting 1 in 4700 male
births. DMD results in loss of ambulation, respiratory failure, cardiomyopathy (CM), and premature death. CM
is the leading cause of death in DMD, but CM progression is variable. Currently, there are no genetic, blood, or
imaging biomarkers that can predict high- or low-risk cardiovascular phenotype. More importantly, there are no
established cardiac outcome measures. Novel, targeted therapeutics are necessary to treat DMD CM, but this
knowledge gap makes clinical trials challenging. A better understanding of CM disease progression is critical to
improve clinical trial efficiency. To address these obstacles, we propose a rigorous, prospective, serial
evaluation in the largest cohort of DMD patients with complete cardiovascular phenotyping. This study will
assess serum and imaging markers of fibrosis as surrogate biomarkers of disease progression and ultimately
mortality. It will leverage the DMD Cardiac Consortium (created as part of the PIs R56), which has
standardized cardiac MRI and skeletal muscle protocols for the assessment of DMD progression. We will
combine this prospective evaluation with a comprehensive assessment of genetic polymorphisms performed
using DNA collected from the largest DMD registry. The central hypothesis of this proposal is that imaging and
blood biomarkers detect subclinical myocardial fibrosis with potential for use as surrogate biomarkers of CM in
DMD. We further hypothesize genotyping in a large sample size of DMD patients can determine the impact of
genetic polymorphisms on DMD CM progression. Aim 1 will collect DNA using the largest DMD registry to
discover genetic variants that determine DMD CM severity. Aim 2 will identify serum biomarkers that
characterize DMD CM disease severity. Aim 3 will define the longitudinal progression of DMD CM in the
current era and determine serum and imaging measures of myocardial fibrosis that herald a subsequent
change in cardiac function. The proposed studies will include four of the larger cardiac muscular dystrophy
centers in the country and will create the largest cohort of DMD patients with rigorous cardiovascular
phenotyping. The consortium has been constructed to allow additional sites to join in order to foster the larger
collaborative efforts necessary to achieve meaningful results in this rare disease. This project directly
addresses the goals of the funding mechanism to characterize the natural history of rare diseases, identify
genotype and phenotype subpopulations, and develop clinical outcome measures. These results will have
clinical relevance for other similar diseases, including Becker muscular dystrophy and female mutation carriers.
The innovation of this grant is the integration of genetic polymorphisms with imaging and blood biomarkers to
identify surrogate biomarkers of cardiovascular disease. The ability to readily test novel and ...

## Key facts

- **NIH application ID:** 10016246
- **Project number:** 5R01FD006649-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Jonathan Harvey Soslow
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2021
- **Award amount:** $577,922
- **Award type:** 5
- **Project period:** 2019-09-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016246

## Citation

> US National Institutes of Health, RePORTER application 10016246, Prospective Development of a Multimodal Biomaker Platform for Predictive Risk Stratification of Cardiac Disease in Duchenne Muscular Dystrophy (5R01FD006649-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10016246. Licensed CC0.

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