# Gene therapy with modified GlcNAc-1-phosphotransferase for mucolipidosis

> **NIH NIH R21** · WASHINGTON UNIVERSITY · 2021 · $433,125

## Abstract

PROJECT SUMMARY/ABSTRACT
Mucolipidosis is a group of inherited conditions in which lysosomal enzymes do not properly traffic to the
lysosomes, due to deficient activity of UDP-N-acetylglucosamine: lysosomal enzyme N-acetyl-glucosamine-1-
phosphotransferase and subsequent failure to add mannose-6-phosphate residues to lysosomal enzymes. As
a result, lysosomes accumulate a variety of substrates that cannot be properly degraded, causing progressive
physical and neurological disease and early death. Meanwhile, soluble lysosomal enzymes, lacking mannose-
6-phosphate, can be found in the bloodstream in abnormally high amounts. There is no available treatment.
Here, using a null mouse model of mucolipidosis type II (also known as “I-cell disease”), we propose to study
gene therapy with a novel S1S3 phosphotransferase for correction of this disorder. We will employ an adeno-
associated viral vector, AAV-9, that has the ability to effect widespread transduction of systemic organs and
brain when administered intravenously to mice. The experiments are designed to address the following
regarding the amenability of mucolipidosis type II to treatment with S1S3 phosphotransferase: 1) biodistribution
of phosphotransferase expression to relevant organs including brain, 2) restoration of mannose-6-
phosphorylation of lysosomal hydrolases, 3) improvement in lysosomal storage, and the distribution of this
effect, 4) improvement in phenotype, including growth and behavior, and 5) lack of apparent toxicity, including
mortality, in treated mice. The project combines complementary expertise in glycosylation and trafficking of
lysosomal proteins, therapy development for lysosomal diseases, and characterization of the mucolipidosis-II
mouse including behavior and pathology.

## Key facts

- **NIH application ID:** 10317695
- **Project number:** 1R21NS124193-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** PATRICIA I DICKSON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $433,125
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10317695

## Citation

> US National Institutes of Health, RePORTER application 10317695, Gene therapy with modified GlcNAc-1-phosphotransferase for mucolipidosis (1R21NS124193-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10317695. Licensed CC0.

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