Blocking the p38 stress protein to help people with Friedreich ataxia
Official title: p38 MAPK activation as a therapeutic target for Friedreich ataxia
Funded at Children's Hosp of Philadelphia · NIH-11325344 · Data updated 2026-11-12
Looks at whether blocking the p38 stress-response protein can improve cell health and reduce nerve and heart damage in people with Friedreich ataxia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Children's Hosp of Philadelphia NIH-funded |
| Lab location | 1 site (Philadelphia, United States) |
| Project start | June 15, 2022 |
| Project end | March 31, 2027 |
| Funding year | 2026 |
| Award (this year) | $556,692 |
| NIH project number | 5R01NS124640-05 |
| Project ID | NIH-11325344 on NIH RePORTER |
Who could benefit from this research
✓Could help
People with genetically confirmed Friedreich ataxia (frataxin deficiency), especially those with nerve or heart involvement, would be the eventual candidates for therapies developed from this work.
✕Less likely to help
Patients whose ataxia is caused by conditions unrelated to frataxin or those with advanced, irreversible tissue loss may be unlikely to benefit from these specific approaches.
What this research studies
From a patient point of view, researchers are studying why cells lacking enough frataxin (the problem in Friedreich ataxia) activate a stress signal called p38 and how that makes mitochondrial iron-sulfur cluster production worse. In the lab they will lower p38 activity directly or reduce what activates it (for example by cutting oxidative damage or DNA damage signaling) and measure whether iron-sulfur cluster biogenesis and cell function improve. The work uses patient-derived cells and model systems, and it tests drug-like inhibitors of p38 and its downstream partner MK2 as well as approaches to reduce lipid peroxidation and DNA damage. Findings could point to treatments or future clinical trials aimed at protecting nerves and heart muscle in FA.
Why it matters
Potential benefit: If successful, this research could lead to new therapies that restore mitochondrial function and slow or prevent neurological and cardiac decline in Friedreich ataxia.
How similar studies have gone: Previous cell and animal studies indicate that blocking p38 or reducing oxidative stress can reverse some FA-related defects, but this approach has not yet been proven in human patients.
Where this research is happening
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Children's Hosp of Philadelphia
Philadelphia, United States Active
Researchers
- Principal investigator: Wilson, Robert B — Children's Hosp of Philadelphia
- Study coordinator: Wilson, Robert B
Related research
Other NIH-funded projects on the same topics.
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Understanding early Friedreich ataxia in children to improve how we measure outcomes
This study looks at how Friedreich ataxia starts and progresses in kids to create better, child-friendly measures for tracking the disease and testing treatments.
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Targeting p38 MAPK to treat Friedreich ataxia
This study is looking at how a specific pathway in the body might be making Friedreich ataxia worse, and it hopes to find new treatments that could help improve symptoms and slow down the disease for those living with it.
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Researchers are creating a patient-derived, human cell model of Purkinje cells to understand why this brain disease causes cerebellar degeneration in people with Ataxia Telangiectasia.
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VEGF-mimetic nanoparticles to help spinocerebellar ataxia type 1
A new, patient-friendly approach is being developed to deliver a VEGF-like therapy using tiny particles that could protect brain cells in spinocerebellar ataxia type 1.
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Targeting FICD to Help Spinocerebellar Ataxia Type 3 (SCA3)
A brain-focused project tests whether blocking FICD, a protein in cells’ ER quality system, can slow or prevent damage in people (via animal and cell studies) who have spinocerebellar ataxia type 3.
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Understanding how unstable GAA repeats affect Friedreich’s ataxia progression
A study in adults and children with Friedreich’s ataxia will look at how changes in GAA repeat length inside the FXN gene relate to the disease’s start and progression.
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.