InterventionsHuman trial40 participantsRandomised trial

Fenofibrate improves cognition in chronic brain injury trial

In a randomized trial of 40 older adults with chronic traumatic brain injury, fenofibrate lowered plasma neurofilament light chain levels and improved cognitive function.

Science Translational Medicine3 Oct 2026, 00:10 BST

In animal models, clinical specimens, and patients, researchers investigated how cranial bone marrow affects chronic traumatic brain injury. In preclinical assays and human specimens, injury prompted persistent myelopoiesis in the cranial bone marrow, causing an expansion of inflammatory monocytes and macrophages that aggravated with aging and migrated into the brain parenchyma. Age-related peroxisome proliferator-activated receptor α (PPARα) deficiency disrupted lipid metabolism in these cells and increased H3K4me3-mediated inflammatory chromatin states. Preclinical activation of PPARα with fenofibrate corrected monocyte lipid metabolism and lowered their infiltration into the brain. In a proof-of-concept randomized clinical trial of 40 older adults with chronic traumatic brain injury, fenofibrate treatment reduced plasma neurofilament light chain levels and improved cognitive functions.

Why it matters

The findings suggest that cranial bone marrow contributes to chronic neuroinflammation that worsens with age after brain trauma. Restoring metabolic regulation in skull-derived immune cells may offer a therapeutic strategy to counter long-term neurological decline in older adults.

Caveats

The clinical evidence comes from an early proof-of-concept trial in 40 older adults, requiring confirmation in larger cohorts. Furthermore, the detailed migration and chromatin mechanisms were identified in animal assays and cell-transfer models.