# Validation of analytical methods for quantification of a pentasaccharide biomarker in efficacy assessment of AVV treatment for GM1 gangliosidosis

> **NIH NIH U01** · WASHINGTON UNIVERSITY · 2022 · $393,750

## Abstract

PROJECT SUMMARY/ABSTRACT
GM1-gangliosidosis is a rare, fatal, neurodegenerative genetic disease caused by the deficiency of β-
galactosidase enzyme activity and characterized clinically by a wide range of variable neurovisceral,
ophthalmological and dysmorphic features. There are currently no effective therapies for GM1-gangliosidosis
and only symptomatic treatments are available. In preclinical models, adeno-associated viral (AAV) gene therapy
that restores the β-galactosidase enzyme activity is the most promising therapy for delaying symptom onset,
reducing storage in the brain and peripheral tissues, and increasing lifespan. These impressive results have
provided the foundation for AAV gene therapy clinical trials. One of the major challenges for developing
treatments for GM1-gangliosidosis is the difficulty in the evaluation of treatment efficacy due to the small and
heterogeneous patient population as well as slow progression in non-infantile patients. Recently we used liquid
chromatography-tandem mass spectrometry (LC-MS/MS) to identify a pentasaccharide (referred to as H3N2b)
that is elevated > 20-fold in patient urine, plasma, and cerebrospinal fluid (CSF), and in the central nervous
system (CNS) of the GM1-gangliosidosis cat. The CNS H3N2b levels in the GM1-gangliosidosis cat are reduced
in response to AAV-treatment. H3N2b has potential as a pharmacodynamics/response biomarker for
assessment of AAV-treatment efficacy in GM1-gangliosidosis. The goal of this proposal is to validate LC-MS/MS
methods for determination of H3N2b in human urine, plasma, CSF, which will be used to assess AAV gene
therapy treatment efficacy in a clinical trial. The aims of this application are 1) validation of LC-MS/MS methods
for quantification of H3N2b in human plasma, urine, and CSF; 2) assessment of H3N2b in samples collected
from GM1-gangliosidosis natural history study; and 3) application of H3N2b for assessment of treatment efficacy
of AAV gene therapy. The proposed work will provide a much-needed tool for assessing therapeutic efficacy.

## Key facts

- **NIH application ID:** 10360564
- **Project number:** 5U01NS114156-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Xuntian Jiang
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $393,750
- **Award type:** 5
- **Project period:** 2021-03-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10360564

## Citation

> US National Institutes of Health, RePORTER application 10360564, Validation of analytical methods for quantification of a pentasaccharide biomarker in efficacy assessment of AVV treatment for GM1 gangliosidosis (5U01NS114156-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10360564. Licensed CC0.

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