# Disease Mechanisms of Pontocerebellar Hypoplasia Type 10

> **NIH NIH R01** · CASE WESTERN RESERVE UNIVERSITY · 2022 · $518,599

## Abstract

PROJECT SUMMARY/ABSTRACT
 Degeneration of brain or spinal cord neurons is associated with many untreatable neurological disorders
and leads to a gradual decline in cognitive and motor function, and eventual death. While more prevalent in aged
individuals, neurodegenerative disease onset is variable and can begin in childhood. There are no effective
therapies for the majority of patients, likely due to our limited understanding of disease etiology. Inherited
neurodegenerative disorders are commonly caused by genetic mutations in RNA binding proteins that regulate
RNA biogenesis. In order to develop therapeutics for this class of disorders, it will be critical to understand how
RNA binding proteins function in normal and diseased states, and whether molecular changes are amenable to
correction.
 Our preliminary data suggests mRNA processing may be significantly affected in cases of inherited
childhood motor neuron degeneration. To test our hypothesis that mRNA processing defects cause pediatric
motor neuron disease, we have created human stem cell- and animal-based models to correlate molecular
changes with disease pathology. We will apply high-throughput sequencing, electrophysiology, histology and
behavioral approaches to our novel disease models to pinpoint pathogenic transcriptional mRNA isoforms
expressed as a consequence of the RNA binding protein mutation as well as test a candidate targeted gene-
based therapy.

## Key facts

- **NIH application ID:** 10428653
- **Project number:** 5R01NS123524-02
- **Recipient organization:** CASE WESTERN RESERVE UNIVERSITY
- **Principal Investigator:** Ashleigh E Schaffer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $518,599
- **Award type:** 5
- **Project period:** 2021-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10428653

## Citation

> US National Institutes of Health, RePORTER application 10428653, Disease Mechanisms of Pontocerebellar Hypoplasia Type 10 (5R01NS123524-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10428653. Licensed CC0.

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