# Reading Frame Correction for the Treatment of Batten Disease

> **NIH NIH R01** · ROSALIND FRANKLIN UNIV OF MEDICINE & SCI · 2021 · $609,223

## Abstract

CLN3 Batten disease is a fatal lysosomal storage disorder (LSD) resulting from autosomal recessive mutations
in CLN3. The disease progresses from vision loss in early childhood to seizures, motor decline, cognitive
disability and dementia, with a typical life expectancy of 15-30 years of age. There is no cure for CLN3 Batten
and the only treatments available address some disease symptoms, but do not delay disease progression. The
discovery of an effective treatment for CLN3 Batten has been hindered by a lack of understanding of the
protein's function and the underlying mechanisms leading to neurodegeneration. The goal of this proposal is to
test a therapeutic approach for CLN3 Batten that employs antisense oligonucleotides (ASOs) and in so doing,
elucidate mechanisms of neurodegeneration in this disease that will inform research and discovery of effective
treatments for Batten diseases and other LSDs. Most cases of CLN3 Batten are caused by deletion of exons 7
and 8 (CLN3Δ78), which results in an open reading frame shift and a premature termination codon. We
hypothesize that using ASOs to redirect pre-mRNA splicing and correct the reading frame of CLN3Δ78 mRNA
will partially restore protein function and have a therapeutic effect in CLN3 Batten disease. Our preliminary
findings support our hypothesis, demonstrating that restoring the CLN3Δ78 reading frame alleviates dysfunction
associated with disease in both cell and animal models. We will test our hypothesis in the proposed project
with the aims to 1) compare the function of the wild type and novel CLN3 isoforms, 2) develop an approach
using ASOs to increase CLN3Δex78 isoforms, 3) assess ASO treatments for CLN3 Batten disease using human
cell lines as well as mouse and 4) porcine models of CLN3 Batten disease. Collectively, this study will allow us
to better understand the function of the CLN3 protein and the utility of ASOs in treating CLN3 Batten disease.

## Key facts

- **NIH application ID:** 10146504
- **Project number:** 5R01NS113233-02
- **Recipient organization:** ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
- **Principal Investigator:** Michelle L Hastings
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $609,223
- **Award type:** 5
- **Project period:** 2020-05-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10146504

## Citation

> US National Institutes of Health, RePORTER application 10146504, Reading Frame Correction for the Treatment of Batten Disease (5R01NS113233-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10146504. Licensed CC0.

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