# Investigating Autophagy in GSD-Ia

> **NIH NIH R56** · DUKE UNIVERSITY · 2020 · $159,202

## Abstract

Glycogen storage disease type Ia (GSD Ia) is an inherited condition characterized by deficiency of glucose-6-
phosphatase (G6Pase). While dietary modification can prevent hypoglycemia in patients, current therapy fails
to prevent long-term complications in many patients, including hepatic lipid accumulation associated with a
high risk for hepatic adenomas that can develop into hepatocellular carcinoma. Our immediate goal is to
develop new therapy for steatosis in models of GSD Ia. Based upon our preliminary studies of
macroautophagy (autophagy) in GSD Ia, we seek to test our central hypothesis: Reversal of abnormalities of
autophagy will reduce accumulated lipids in the GSD Ia liver. Therefore, we propose to study the
hepatocellular abnormalities of GSD Ia, with the goal of developing new therapies for fatty liver by achieving
the following two Specific Aims: 1) Identify the mechanism by which steatosis suppresses autophagy in GSD
Ia, and 2) Evaluate genome editing to prevent long-term complications of GSD Ia. These aims may provide
new treatments by repurposing approved drugs with known safety profiles. Furthermore, the interaction of drug
therapy with potentially curative genome editing will be investigated, with the goal of permanently reversing the
hepatocellular abnormalities of GSD Ia. If successful in GSD Ia, developing therapies that reduce hepatic lipid
accumulations also could be effective at reversing steatosis in other conditions, including metabolic liver
diseases and non-alcoholic fatty liver disease.

## Key facts

- **NIH application ID:** 10241856
- **Project number:** 2R56DK105434-05
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Dwight D Koeberl
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $159,202
- **Award type:** 2
- **Project period:** 2015-12-15 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10241856

## Citation

> US National Institutes of Health, RePORTER application 10241856, Investigating Autophagy in GSD-Ia (2R56DK105434-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10241856. Licensed CC0.

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