# Role of viral infections in potassium channel-related cerebellar ataxia

> **NIH NIH R01** · YALE UNIVERSITY · 2022 · $540,244

## Abstract

Cerebellar ataxia is a progressive neurodegenerative disease with major impact on the daily life of affected
people, their families, and, on the health care system. There is no cure for cerebellar ataxia regardless of its
origin. There is no effective treatment to slow the progression of symptoms that frequently lead to premature
death. Ion channels have been implicated in the etiology of several form of cerebellar ataxia. For example,
specific mutations in KCNC3, the gene encoding the Kv3.3 channel, such as the G592R point mutation, have
been identified as the underlying genetic cause of late-onset spinocerebellar ataxia. Despite of these
developments, there is no understanding of why late-onset cerebellar ataxias emerge in some but not all subjects
with genetic mutations. There is also great variability in when during the lifespan of the affected subjects the
symptoms emerge. Based on our unexpected preliminary observations, we hypothesize that disease onset in
genetically vulnerable subjects is determined by host-pathogen interactions with particular emphasis on viral
infections. Specifically, we assert that the synergistic activation of an intracellular signaling pathway that is
targeted by both the mutant potassium channel and by viral defense mechanisms, impairs cellular function and
results in the death of Purkinje cells. Our hypothesis and preliminary data challenge contemporary views on the
etiology of cerebellar ataxia with implications for novel therapeutic strategies. We will test our hypothesis using
cellular- and animal models with state-of-the-art neurobiological, molecular biological and immunobiological
approaches.

## Key facts

- **NIH application ID:** 10412975
- **Project number:** 5R01NS111242-04
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** AKIKO IWASAKI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $540,244
- **Award type:** 5
- **Project period:** 2019-09-18 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10412975

## Citation

> US National Institutes of Health, RePORTER application 10412975, Role of viral infections in potassium channel-related cerebellar ataxia (5R01NS111242-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10412975. Licensed CC0.

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