# Disease Modeling of Skeletaland Cardiac Muscle in DMD/BMD using Patient-Specific iPS Cells

> **NIH NIH R21** · UNIVERSITY OF MINNESOTA · 2022 · $204,600

## Abstract

Summary
This project aims to establish a reliable platform to use patient-specific induced pluripotent stem (iPS) cells to
model Duchenne Muscular Dystrophy (DMD) and Becker MD (BMD) in the Petri dish, allowing not only for better
insight on the pathogenesis of dystrophin-associated disorders, but specially for the development of a relevant
system for drug screening. Reprogramming technology provides an unprecedented opportunity to generate large
numbers of patient-specific cell types for in vitro disease modeling and drug discovery. Accordingly, iPS cells
have been used extensively for these purposes for several disorders, including amyotrophic lateral sclerosis,
long-QT syndrome, and spinal muscular atrophy, among others. However to date, there has been scarce
literature on the use of this approach to model skeletal muscle disorders, and none studying both skeletal and
cardiac muscle in the context of DMD and BMD.
Our research group has pioneered methods to derive large quantities of skeletal myogenic progenitor cells from
mouse and human pluripotent stem cells, and validated these in vitro and in vivo. Specifically relevant for this
proposal, we have recently published a paper focusing on the in vitro maturation of iPS cells towards the skeletal
muscle lineage (eLIFE, 2019), which is critical for proper disease modeling. For this project, we have samples
from ten DMD/BMD patients, encoding various distinct mutations and displaying mild to severe phenotypes. iPS
cells from these samples will be used to produce large numbers of DMD/BMD skeletal myotubes and
cardiomyocytes. The hypothesis behind this project is that we will be able to recapitulate disease phenotypes in
vitro, including membrane fragility, calcium handling, contraction using three-dimensional myobundles, and
electrophysiology measurements. We foresee that molecular/biological signatures resulting from this work will
not only enhance our understanding of the pathophysiology behind DMD/BMD, but may also serve as in vitro
screening for potential treatments. To validate this hypothesis, we will have control cohort samples, in which we
genetically introduce selected DMD mutations in unaffected iPS cells and/or correct selected DMD mutations.
The work we propose here, of not only generating skeletal and cardiac muscle from iPS cells but also studying
the underlying biology, holds tremendous potential for exploring phenotypes of different mutations, in vitro
disease modeling in general, and drug discovery.

## Key facts

- **NIH application ID:** 10390553
- **Project number:** 1R21AR079236-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Rita C. R. Perlingeiro
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $204,600
- **Award type:** 1
- **Project period:** 2022-03-07 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10390553

## Citation

> US National Institutes of Health, RePORTER application 10390553, Disease Modeling of Skeletaland Cardiac Muscle in DMD/BMD using Patient-Specific iPS Cells (1R21AR079236-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10390553. Licensed CC0.

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