# Study and Treatment of Mitochondrial DNA Depletion Syndrome 3 Using iPSCs

> **NIH NIH R01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2022 · $494,836

## Abstract

Project Summary
We have previously described a procedure that allows us to efficiently differentiate cells with
hepatocyte characteristics from human induced pluripotent stem cells. We have also shown that
iPSCs derived from patients with inborn errors of hepatic metabolism can be used to model
metabolic liver disease in culture. Here we propose to use this approach to study a rare
disease called Mitochondrial DNA Depletion Syndrome 3 (Hepatocerebral type) (MTDPS3) that
is caused by mutations in the Deoxyguanine Kinase (DGUOK) gene. We propose to generate
iPSC-derived hepatocytes that contain different mutations in DGUOK and compare the effect of
these mutations on mtDNA copy number, mitochondrial activity, and hepatocyte function.
Finally, we propose to use these cells as a platform to identify drugs that can be used to treat
MTDPS3 and potentially other mitochondrial DNA depletion syndromes.

## Key facts

- **NIH application ID:** 10320046
- **Project number:** 5R01DK119728-04
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** STEPHEN A DUNCAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $494,836
- **Award type:** 5
- **Project period:** 2019-01-15 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320046

## Citation

> US National Institutes of Health, RePORTER application 10320046, Study and Treatment of Mitochondrial DNA Depletion Syndrome 3 Using iPSCs (5R01DK119728-04). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10320046. Licensed CC0.

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