Targeting mitochondrial DNA repair defects in FUS-ALS with neuron-specific DNA Ligase I therapy
Official title: Targeting Mitochondrial DNA Repair Defects in FUS-Associated ALS via Neuron-Specific DNA Ligase I Replacement
Funded at Methodist Hospital Research Institute · NIH-11507053 · Data updated 2026-11-12
A patient-facing study aims to test a neuron-directed therapy that helps nerve cells repair their mitochondrial DNA in people with ALS linked to FUS mutations.
Quick facts
| Grant type | R03 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Methodist Hospital Research Institute NIH-funded |
| Lab location | 1 site (Houston, United States) |
| Project start | September 11, 2026 |
| Project end | August 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $161,500 |
| NIH project number | 1R03NS153153-01 |
| Project ID | NIH-11507053 on NIH RePORTER |
Who could benefit from this research
✓Could help
Ideal candidates are individuals with FUS-related ALS/FTD spectrum where mitochondrial DNA repair deficits are implicated.
✕Less likely to help
Patients without FUS mutations or without mitochondrial repair defects may not benefit from this approach.
What this research studies
This project explores a new treatment approach focused on neurons to repair mitochondrial DNA damage caused by FUS-related ALS. It uses a gene-delivery strategy to supply DNA Ligase I specifically to brain cells to fix mitochondrial DNA breaks and restore energy production. The research will be conducted in a controlled setting to see if this repair improves neuron health and function in models that mimic the human disease. If successful, this could lay groundwork for future therapies targeting mitochondrial problems in ALS. The focus is on translating basic findings into a potential patient-facing option for a specific ALS subset.
Why it matters
Potential benefit: If successful, it could improve nerve cell health and energy in people with FUS-associated ALS, potentially slowing disease progression.
How similar studies have gone: Prior work has shown that targeting mitochondrial repair can improve cellular function in related models, supporting further exploration.
Where this research is happening
-
Methodist Hospital Research Institute
Houston, United States Active
Researchers
- Principal investigator: Hegde, Muralidhar L — Methodist Hospital Research Institute
- Study coordinator: Hegde, Muralidhar L
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.