# Targeted Proteomic Analysis of Extremely Low Abundance Signature Peptide Biomarkers for Potential Newborn Screening in Wilson's Disease

> **NIH NIH R21** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $235,375

## Abstract

Project Summary
Wilson Disease (WD) is an autosomal recessive disorder caused by mutations in the ATP7B gene, which
encodes an intracellular copper-transporting ATPase, and results in copper accumulation within the body. WD
has an estimated incidence of 1 in 30,000 individuals. WD is present and asymptomatic at birth. Patients, when
untreated, develop irreversible brain damage and liver cirrhosis. Early treatment is effective in preventing these
negative sequelae and greatly improves patient quality of life. This makes early detection and treatment of WD,
ideally in the neonatal period, of paramount importance to achieving the best long-term clinical outcomes.
Newborn screening (NBS) to identify infants with treatable congenital disorders is carried out worldwide and
has led to a significant increase in early diagnosis of many diseases which require early intervention.
Unfortunately, no cost-effective newborn screening methods are currently available for early detection of WD.
We recently demonstrated that peptide immunoaffinity enrichment coupled to SRM (immuno-SRM) can
quantify peptide biomarkers in dried blood spots (DBS) and that the assay can readily distinguish affected
cases from controls (R01AI123135-01) [1]. This immuno-SRM approach has opened up the possibility of using
a multiplexed immuno-SRM approach to screen a variety of congenital disorders using proteins as biomarkers
in DBS.
Our ultimate goal is to develop a high-throughput quantitative assay for NBS of WD using DBS. We recently
developed an immuno-SRM assay to quantify a low level target peptide for ATP7B, a potential marker protein
for WD, in DBS [1]. The objective of this application is to enrich our current assays with additional WD
biomarkers, develop quality control (QC) measures, and validate the assay in a large cohort of patients and
carriers from a broad spectrum of mutations, regions and ethnicities. Our central hypothesis is that in most of
these genetically confirmed WD patients, the levels of ATP7B protein in DBS would be absent or reduced; and
that the immuno-SRM assay can readily differentiate affected patients from controls or proven carriers.
Our specific aims are to: 1: Enhance the sensitivity and specificity by multiplexing crucial marker
peptides of ATP7B with the existing well-characterized immuno-SRM assay. Monitoring multiple peptides
of ATP7B protein by immuno-SRM using multiple monoclonal antibodies will help increase sensitivity and
specificity. 2. Assess the ability of a multiplexed immuno-SRM to identify WD patients in a large set of
clinical samples with a broad spectrum of mutations, regions and ethnicities. Here, we will validate QC
process measures through the establishment of reference ranges for existing QC peptides. We will examine
the hypothesis that the immuno-SRM can correctly identify patients with WD and suitability for NBS. We will
(1) by establish reference ranges from a total of 400 controls with various age groups and (2) analyze pati...

## Key facts

- **NIH application ID:** 9890920
- **Project number:** 5R21HD097558-02
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Sihoun Hahn
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,375
- **Award type:** 5
- **Project period:** 2019-03-15 → 2021-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890920

## Citation

> US National Institutes of Health, RePORTER application 9890920, Targeted Proteomic Analysis of Extremely Low Abundance Signature Peptide Biomarkers for Potential Newborn Screening in Wilson's Disease (5R21HD097558-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890920. Licensed CC0.

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