# The role of UBE3A in gliopathic seizures

> **NIH NIH R01** · TULANE UNIVERSITY OF LOUISIANA · 2024 · $367,677

## Abstract

As many as ~3 million individuals suffer from epileptic seizures in the US alone. Although some forms of epilepsy
respond quite well to anti-seizure medications, a substantial portion of individuals suffering from epilepsy do not
respond well to medication or dietary treatments. One way to investigate the underlying molecular and cellular
pathology of seizure disorder is by studying a genetically defined syndrome where epilepsy is a prominent feature.
Approximately 25-50% of individuals with Duplication 15q syndrome (Dup15q) suffer from difficult to control
seizures. The prevailing hypotheses to explain seizures in Dup15q are maternal specific neuronal elevation of
the ubiquitin E3 ligase UBE3A and/or duplication of a cluster of GABA receptor genes located adjacent to UBE3A
at 15q11.2-q13.1. Studies using the fruit fly, Drosophila melanogaster, from our laboratory indicates that these
seizures may be caused by elevated levels of UBE3A in glia, not neurons as previously proposed. The premise
for this proposal is that seizures are caused by elevated levels of the UBE3A protein in glia, not neurons,
providing not only a pathway to molecular mechanism for Dup15q related epilepsy, but also a paradigm shift,
directly implicating glial cells in the etiology of seizures. The experiments outlined in this proposal are designed
to investigate the developmental timing and molecular changes in glial cells over-expressing Dube3a and to
reveal how these changes are recapitulated in a new mouse model we developed that expresses Ube3a in glial
cells. Everything we learn from these studies in flies will be directly disseminated to a team of seizure experts
who work at the Duplication 15q centers of excellence throughout the country. The identification of new
therapeutic targets for Dup15q epilepsy may also provide new treatment options to individuals who are
pharmacoresistant to current anti-epileptics.

## Key facts

- **NIH application ID:** 11243907
- **Project number:** 7R01NS115776-06
- **Recipient organization:** TULANE UNIVERSITY OF LOUISIANA
- **Principal Investigator:** LAWRENCE T REITER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $367,677
- **Award type:** 7
- **Project period:** 2020-09-30 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11243907

## Citation

> US National Institutes of Health, RePORTER application 11243907, The role of UBE3A in gliopathic seizures (7R01NS115776-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11243907. Licensed CC0.

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