Blocking the p38 stress protein to help people with Friedreich ataxia

p38 MAPK activation as a therapeutic target for Friedreich ataxia

NIH-funded research Children's Hosp of Philadelphia · NIH-11325344

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 typeR01 grant
Study typeNIH-funded research
Funding institutionChildren's Hosp of Philadelphia NIH-funded
Lab location1 site (Philadelphia, United States)
Project IDNIH-11325344 on NIH RePORTER

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.

Who could benefit from this research

Good fit: 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.

Not a fit: 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.

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 performed: 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

Philadelphia, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.