# Diagnosis & Biomarker Discovery Project

> **NIH NIH U54** · MAYO CLINIC ROCHESTER · 2022 · $408,029

## Abstract

DIAGNOSTICS AND BIOMARKER DISCOVERY-ABSTRACT/PROJECT SUMMARY
Congenital disorders of glycosylation (CDG) have rapidly developed into one of the largest group of metabolic
disorders, yet they are poorly described without natural histories, affective treatment, validated biomarkers
correlating with disease severity and without comprehensive diagnostic tools. PMM2-CDG and congenital disorders
of galactosylation (e.g. SLC35A2-CDG, PGM1-CDG) are the most common N-glycosylation disorders with
emerging potential therapies. Congenital disorders of de-glycosylation is a recently discovered group of abnormal
glycosylation with a potential noninvasive diagnostic biomarker in NGLY1 deficiency. Some long-known CDG types,
like ALG13-CDG however still have no reliable, validated diagnostic methods. Our overall objective and
overreaching aim is to develop and validate new biochemical diagnostic techniques and therapeutic biomarkers for
future CDG clinical trials. We will overcome the shortcomings of current biochemical techniques and biomarkers in
measuring therapeutic efficacy and diagnostics of specific CDG. To address the unmet need and accomplish our
overall objective, we will 1) develop and validate biomarkers to monitor therapeutic efficacy in clinical trials for
PMM2-CDG; 2) develop quantitative biomarkers to diagnose PGM1-CDG and monitor galactose therapy efficacy;
3) develop quantitative biomarkers to diagnose SLC35A2-CDG and monitor galactose therapy efficacy; 4) validate
biomarker to diagnose and follow NGLY1 deficiency and monitor N-acetylglucosamine (GlcNAc) therapy response;
5) validate novel diagnostic biomarkers for ALG13-CDG; 6) qualify and admit new patients to the general CDG
population. The impact of this aim on the CDG community is twofold. We will significantly improve diagnostics of
patients with CDG, and through improved diagnostics and identification of biomarkers we will increase clinical trial
readiness. Achieving these aims should enable us to correlate disease progression and disease severity (Project 1)
and their response to therapy (Project 3) with quantifiable biochemical assays. Parallel measurements of the same
biomaterial at the different laboratories will not only increase reliability, but will be integral to the validation process
and facilitate the process of developing standard biochemical test for diagnosis of the disorders. Such improved
diagnostics will be important to assess disease severity and through validation of biochemical outcome measures
or biomarkers our efforts will support upcoming clinical trials in CDG. The multiple approaches using state-of-the-
art technologies will provide data to assess the overall success of the project. Moreover, the biochemical validations
may provide a framework for assessing other emerging or yet-to-be identified glycosylation disorders.

## Key facts

- **NIH application ID:** 10480835
- **Project number:** 5U54NS115198-04
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Hudson H. Freeze
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $408,029
- **Award type:** 5
- **Project period:** 2019-09-15 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10480835

## Citation

> US National Institutes of Health, RePORTER application 10480835, Diagnosis & Biomarker Discovery Project (5U54NS115198-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10480835. Licensed CC0.

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