# Implications of Genetic Diversity in Muscular Dystrophy

> **NIH NIH DP2** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $427,964

## Abstract

ABSTRACT
Differences in our individual genomes give rise to most of human diversity. This uniqueness of every human
being underpins the purpose of precision medicine, which posits that disease prediction, diagnosis, and
treatment for each individual is based on personal genomic variations. The rapid advancement of genome
editing technology has led to numerous promising preclinical studies in muscular dystrophies (MDs). These
studies were performed in inbred animals, with mice being the most extensively used models, in which the
component of genetic diversity has been largely ignored. Genetically speaking, developing a therapeutic
intervention in a single inbred mouse strain is the equivalent of treating a single patient and limits the
generalizability and translatability of the results into human applications. Failure to anticipate the genetic
diversity in patient populations will confound future clinical trials and may lead to adverse outcomes.
In this NIH Innovator Award, my goal is to revolutionize the conventional method by which we develop genetic
therapy to reflect diverse and more realistic human populations. First, I will integrate the naturally occurring
genetic reference panel into a model harboring MD-causing mutation to better simulate diverse patient
population and elevate its translational value. I will use this innovative model to investigate whether the
introduced genetic variation profoundly modifies the neuromuscular presentations. Furthermore, I will study
the implications of genetic variation on the safety and efficacy of therapeutic genome editing approaches that
I have developed throughout my career.
As we move closer towards designing clinical treatment that is based on an individual's biological makeup, it
is imperative that we understand how inherited variability influences disease phenotypes, how it can confound
experiments, and how it can be exploited to reveal new truths about disease biology. Using MD as a starting
point, successful outcome of this project can be integrated into a framework for future therapeutic
developments in different diseases and across patient populations.

## Key facts

- **NIH application ID:** 11065745
- **Project number:** 4DP2AR081047-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Dwi Utami Kemaladewi
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,964
- **Award type:** 4N
- **Project period:** 2021-09-01 → 2025-04-17

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11065745

## Citation

> US National Institutes of Health, RePORTER application 11065745, Implications of Genetic Diversity in Muscular Dystrophy (4DP2AR081047-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/11065745. Licensed CC0.

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