Small molecule therapy to turn on the paternal UBE3A gene in Angelman syndrome
Official title: Small Molecule Therapeutic Discovery for Angelman Syndrome
Funded at Univ of North Carolina Chapel Hill · NIH-11353907 · Data updated 2026-11-12
A small molecule drug is being developed to turn on the paternal UBE3A gene in Angelman syndrome, with the goal of improving brain function.
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 | June 1, 2023 |
| Project end | May 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $562,899 |
| NIH project number | 5R01NS131615-04 |
| Project ID | NIH-11353907 on NIH RePORTER |
Who could benefit from this research
✓Could help
Individuals with Angelman syndrome or those with maternal UBE3A deletions or related genetic features could be future trial candidates.
✕Less likely to help
Patients without Angelman syndrome or lacking the specific paternal UBE3A unsilencing mechanism may not benefit.
What this research studies
This project targets Angelman syndrome, a neurodevelopmental condition caused by loss of the maternal UBE3A gene. Researchers have identified a small molecule that can unsilence the paternal UBE3A gene in neurons, and it has shown brain-wide protein expression in mouse models without obvious toxicity. The work will test whether the compound can reverse behavioral and brain activity abnormalities in Angelman model mice, and will explore how the molecule works and how to improve its properties. If successful, the study could pave the way for non-invasive treatments and future clinical trials for people with Angelman syndrome.
Why it matters
Potential benefit: If effective, this approach could restore UBE3A function in the brain and reduce core symptoms of Angelman syndrome, potentially improving development and quality of life.
How similar studies have gone: Early studies in model systems show promise for unsilencing paternal UBE3A and improving phenotypes, supporting further development.
Where this research is happening
-
Univ of North Carolina Chapel Hill
Chapel Hill, United States Active
Researchers
- Principal investigator: Philpot, Benjamin D — Univ of North Carolina Chapel Hill
- Study coordinator: Philpot, Benjamin D
Related research
Other NIH-funded projects on the same topics.
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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.
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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.
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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.
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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.
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UBE3A mosaicism and Angelman syndrome phenotypes
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.
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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.