# Bridging the translational divide from cells to patients: toward reliable neuromarkers of Batten disease

> **NIH NIH P50** · UNIVERSITY OF ROCHESTER · 2020 · $274,644

## Abstract

PROJECT SUMMARY
Neuronal Ceroid Lipofuscinoses (NCLs) are a group of neurodevelopmental diseases categorized as
autosomal recessive lysosomal storage disorders. Clinical features include retinopathy, intracellular
accumulation of lysosomal ceroid and lipofuscin, seizures, motor decline and dementia. CLN3 disease
(Juvenile Neuronal Ceroid Lipofuscinosis, JNCL) is one of the most common types of NCL, and results from
mutations in the CLN3 gene on chromosome 16. Individuals with the CLN3 mutation show a consistent decline
in cognitive functioning and verbal intellectual abilities over the course of later childhood and early
adolescence. The precise neuropathological bases of this decline are not yet well understood and objective
neurologic biomarkers (neuromarkers) of disease progression are not currently available. Yet, our preliminary
data indicate that a good candidate for a biomarker of CLN3 disease that tracks with disease severity can be
identified using high-density electroencephalography (EEG) in the context of auditory mismatch negativity
experiments. Using these methods we have been able to show consistent declines in the P1 component of the
auditory evoked response as CLN3 disease severity increases.
 Here we propose to further develop our understanding of auditory processing in children and young adults
with CLN3 disease with a focus on validating a biomarker of the disease. Simultaneously we propose to use a
mouse model of CLN3 disease with the same genetic mutation to identify an endophenotype that is shared in
both patients and mice. We will also test whether the accumulation of autofluorescent lipopigments
preferentially occur in specific subsets of interneurons and predict their subsequent loss as well as the
hypertrophy of remaining interneurons. This three-pronged, convergence of techniques and approaches in
both species has the potential to yield unique opportunities to understand the underlying neurophysiology of
CLN3 mutations and their impact on auditory processing, as well as encourage testing of future treatments for
CLN3 disease first in mice and secondarily in patients. This innovative approach, tying the patient
neurophysiological markers to identical measures in the murine model of the disease will permit improved and
more efficient pre-clinical development of novel therapeutics, improved measurement of disease progression in
clinical trials, and with these advances, lead to improved outcomes for patients with CLN3 mutations.

## Key facts

- **NIH application ID:** 10085501
- **Project number:** 1P50HD103536-01
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Kuan Hong Wang
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $274,644
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10085501

## Citation

> US National Institutes of Health, RePORTER application 10085501, Bridging the translational divide from cells to patients: toward reliable neuromarkers of Batten disease (1P50HD103536-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10085501. Licensed CC0.

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