An old cholesterol drug partly rescued failing mitochondria in Leigh syndrome models — in cells and mice
Edited by Samael A. Tejada, Founder & Editor-in-Chief
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Bezafibrate, an old generic lipid drug, partially rescued complex I mitochondrial failure in Leigh syndrome models — cultured cells and mice — an Orphanet Journal of Rare Diseases study reports (November 11, 2026). The rescue was partial, the mouse model was drug-induced rather than genetic, and there is no human evidence yet.
Leigh syndrome has no approved treatment, so any credible lead matters. This one comes from an unlikely shelf: a generic cholesterol drug old enough to be off-patent for decades.
What models did the study use?
Two complementary models of complex I failure. In cultured L929 fibroblast cells, the team knocked down NDUFAF2 — a factor mitochondria need to assemble complex I — which impaired viability, promoted cell death and caused marked mitochondrial dysfunction. In mice, the complex I inhibitor rotenone produced a Leigh-like picture: weight loss, reduced food and water intake, motor dysfunction and shortened survival.
What did bezafibrate do?
In cells, bezafibrate partially rescued the dysfunction caused by NDUFAF2 knockdown — partial is the authors' own framing, not a full restoration. In the rotenone-treated mice, the Leigh-like features were significantly attenuated. The authors link the effect to complex I homeostasis, receptor-mediated mitophagy and an MCHR1/CRHR2–cAMP signalling axis. The abstract reports the effects qualitatively, without effect sizes.
What are the limits?
Leigh syndrome in children is genetic; the mouse model here was created with a toxin, not a gene. The authors themselves say the findings warrant investigation in genetically defined models. Bezafibrate is a real, widely used drug with a known safety record in lipid care, which makes follow-up easier — but nothing in this paper shows it helps a person with Leigh syndrome.
Frequently asked questions
What is Leigh syndrome?
A severe mitochondrial disease, usually appearing in infancy or early childhood, that damages the brain and muscles. It is most often caused by defects in mitochondrial energy production, frequently complex I.
What is complex I?
The first and largest machine in the mitochondrial electron transport chain — the assembly line that converts food energy into ATP, the cell's usable energy currency.
Is bezafibrate available now?
Yes, as a generic drug for lipid disorders in many countries. That does not make it a Leigh syndrome treatment: the evidence here is preclinical, and any use for mitochondrial disease would be off-label and unproven.
Where the evidence stands
- Established: Leigh syndrome is a severe, usually childhood-onset mitochondrial disease frequently involving complex I failure; it has no approved disease-modifying treatment. Bezafibrate is an established generic lipid drug.
- Preliminary: The rescue effect: one preclinical study (Orphanet Journal of Rare Diseases, 2026) in knockdown cells and a toxin-induced mouse model, reported qualitatively.
- Absent: Evidence in genetically defined Leigh models or in human patients.
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