# Identification of glycosaminoglycans for newborn screening and therapeutic monitoring of mucopolysaccharidoses

> **NIH NIH R44** · BAEBIES, INC. · 2020 · $194,426

## Abstract

ABSTRACT
 Identification of glycosaminoglycans for newborn screening and therapeutic monitoring of
mucopolysaccharidoses
Mucopolysaccharidoses (MPS) are a group of 11 rare inherited metabolic diseases, each caused by a deficiency
in a specific enzyme necessary for the breakdown of complex sugars termed glycosaminoglycans (GAGs). The
accumulation of GAGs in various tissues causes a spectrum of health problems, including heart, bone, joint, and
nervous system complications, which progressively worsen and lead to restricted mobility and premature death.
Therefore, it is critical that affected newborns are identified at birth through newborn screening (NBS). However,
only assays for MPS I and II are currently available in the U.S., and not all states are presently screening for
MPS diseases. A methodology that can screen for MPS disorders, and identify by subtype, would be of
tremendous value to the NBS community; future pilot data from a longitudinal study with such a platform would
provide evidence needed to recommend uniform NBS for MPS disorders with approved therapies. The majority
of currently available treatments result in a reduction in GAG accumulation and therefore monitoring of GAG
levels is a crucial component of MPS treatment regimes. Standard tests for total GAG measurement are currently
performed on urine samples using tandem mass spectrometry (MS/MS) or dimethyl methylene blue and have
several limitations including: poor sensitivity, large sample volumes, and long turnaround times (>3 days).
To overcome these challenges in NBS and therapeutic monitoring for MPS, we propose to develop a
novel high-throughput digital microfluidic (DMF) platform for identification of GAGs that can be
leveraged to screen for disease AND monitor disease treatment. We will use a combination of novel (patent
pending) enzyme modulation assays to measure 1) total GAG levels (to identify if MPS disease is present during
NBS) and 2) specific GAG categories (to determine which specific GAG is elevated during NBS). Application of
targeted next generation sequencing (tNGS) as a 3rd test will determine which specific MPS/subtype is present.
The GAG modulation assays will be performed on our automated DMF cartridge and platform, which can perform
the GAG analyses either on dried blood spot (screening) or whole blood sample (therapeutic monitoring). The
tNGS analysis will be developed in our in-house CLIA-certified laboratory.
We previously demonstrated feasibility of GAG microtiter plate assays for heparan, dermatan, and keratan
sulfates. We will develop assays for total GAGs and chondroitin sulfate, and translate all GAG assays to the
DMF platform. The tNGS gene panel will also be developed for use during NBS. Preliminary analytical
performance of the assay panel will be assessed, and a method comparison is planned against the gold standard
assays to demonstrate platform equivalence. Our innovative and groundbreaking solution for identification of
GAGs will dramatic...

## Key facts

- **NIH application ID:** 10010423
- **Project number:** 1R44HD102242-01
- **Recipient organization:** BAEBIES, INC.
- **Principal Investigator:** Rainer Ng
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $194,426
- **Award type:** 1
- **Project period:** 2020-09-01 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010423

## Citation

> US National Institutes of Health, RePORTER application 10010423, Identification of glycosaminoglycans for newborn screening and therapeutic monitoring of mucopolysaccharidoses (1R44HD102242-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10010423. Licensed CC0.

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