UBE3A mosaicism and Angelman syndrome phenotypes
Official title: UBE3A mosaicism and its relationship to Angelman syndrome phenotypes
Funded at Univ of North Carolina Chapel Hill · NIH-11343229 · Data updated 2026-11-12
A study from UNC Chapel Hill will explore how the mix of neurons with active paternal UBE3A affects Angelman syndrome symptoms using a special mouse model and gene therapy tools.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Univ of North Carolina Chapel Hill NIH-funded |
| Lab location | 1 site (Chapel Hill, United States) |
| Project start | August 14, 2026 |
| Project end | May 31, 2031 |
| Funding year | 2026 |
| Award (this year) | $615,286 |
| NIH project number | 1R01NS148408-01 |
| Project ID | NIH-11343229 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are individuals with Angelman syndrome or researchers seeking to translate these findings into human therapies.
✕Less likely to help
Patients without Angelman syndrome or those not connected to gene-therapy research may not directly benefit.
What this research studies
This project uses a genetically engineered mouse to mark which brain cells express paternal UBE3A and to change how many of those cells are active. Researchers will deliver an AAV-Cas9 gene therapy vector to adjust the percentage of neurons with functional UBE3A and then observe changes in behavior and brain biology. The goal is to map how partial restoration of UBE3A in brain cells relates to symptom severity, guiding future therapies for Angelman syndrome.
Why it matters
Potential benefit: If successful, the work could define how many neurons need UBE3A to be active to improve symptoms, informing future treatments for Angelman syndrome.
How similar studies have gone: Previous work showed partial rescue in mice and some mosaic human data suggesting potential benefit, but the precise relationship remains unknown.
Where this research is happening
-
Univ of North Carolina Chapel Hill
Chapel Hill, United States Active
Researchers
- Principal investigator: Zylka, Mark J. — Univ of North Carolina Chapel Hill
- Study coordinator: Zylka, Mark J.
Related research
Other NIH-funded projects on the same topics.
-
Genome editor therapy for Angelman syndrome in young children
A University of North Carolina team is exploring a gene-editing approach to turn on the silent UBE3A gene in people with Angelman syndrome to reduce symptoms.
-
MicroRNA pathways in Angelman Syndrome: novel targets for therapy
A small study explores how specific microRNAs may influence Angelman syndrome and whether targeting them could lead to new treatments.
-
Delta brain rhythms in Angelman syndrome
Scientists will study unusual brain wave patterns in Angelman syndrome to understand how these signals relate to behavior and guide future treatments for affected children and adults.
-
Targeting the stress response in Angelman syndrome
Aims to understand how loss of a brain gene called UBE3A disrupts pathways in Angelman syndrome and to design therapies that calm the stress response in affected neurons.
-
Small molecule therapy to turn on the paternal UBE3A gene in Angelman syndrome
A small molecule drug is being developed to turn on the paternal UBE3A gene in Angelman syndrome, with the goal of improving brain function.
-
How body‑sensing nerves affect walking in Angelman syndrome
This project looks at whether problems with a nerve sensor called PIEZO2 cause balance and walking problems in people with Angelman syndrome.
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.