# Exploration of salivary huntingtin for biomarker discovery

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $193,125

## Abstract

The mutation responsible for Huntington's disease (HD) is an abnormal CAG repeat expansion in the
HTT gene, which encodes the protein, huntingtin (Htt). Despite HD being a single gene disorder,
there is enormous variability in disease onset, severity of symptoms and course of illness.
Pathogenesis of HD is largely associated with expression of the mutant Htt (mHtt) protein making it
the most significant molecular target for disease modifying therapies. Several therapeutic approaches
aimed at its expression, processing, or turnover are under intense development and already in clinical
trials. Hence, measures of Htt/mHtt have broad potential as a biomarker, provided that levels can be
reliably measured in a surrogate tissue/fluid. Since non-invasive methods to quantify Htt in the CNS
do not exist, measuring the amount of Htt in peripheral cells represents an important step in biomarker
discovery for HD. Although Htt/mHtt has been successfully measured in CSF and blood, the
collection of these fluids is invasive, and repeated sampling can be cumbersome. Alternatively, we
propose to use saliva as a source for measuring Htt/mHtt. As a biospecimen, saliva is an
improvement over blood sampling due it its ease of collection, non-invasive nature, lack of need for
trained personnel and it is amenable to repeated sampling. Importantly, many molecules found in the
human brain that are relevant to CNS function have also been identified in saliva, such as growth
factors, neurotransmitters and even pathological proteins, such as phosphorylated tau and α-
synuclein. In our preliminary studies, we found that salivary levels of total Htt (both normal and mutant
forms) can be reproducibly and reliably measured in human saliva using Western blotting and ELISA
methodologies. We further showed that total Htt protein levels were elevated in saliva samples from
HD patients compared to control individuals and that salivary levels of total Htt were correlated with
motor symptoms in HD patients. In the current proposal, we propose to extend these studies to
measure mutant-only forms of the Htt protein and to identify the predominant forms of Htt in saliva,
with an overall goal to characterize the utility of salivary Htt/mHtt for biomarker purposes in HD (a
single Aim 1). These Aim 1 studies will include: 1). identifying the major forms of Htt/mHtt protein in
saliva; 2). quantifying Htt/mHtt in saliva from HD patients using immunoassays; 3). correlating salivary
Htt/mHtt levels with clinical data; and 4). determining the association between salivary Htt/mHtt levels
and those measured from other sources, including serum, white blood cell fractions and buccal cells.
Salivary readouts of Htt/mHtt could be especially useful in assessing the effects of systemically
delivered HTT-lowering therapies, or detecting peripheral effects of centrally delivered therapies.

## Key facts

- **NIH application ID:** 9842018
- **Project number:** 5R21NS111655-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** ELIZABETH A THOMAS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842018

## Citation

> US National Institutes of Health, RePORTER application 9842018, Exploration of salivary huntingtin for biomarker discovery (5R21NS111655-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842018. Licensed CC0.

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