Dasatinib and quercetin reduce liver fibrosis in a phase-2 MASH trial
The senolytic combination improved liver fibrosis without disease worsening in nearly half of treated participants while lowering cellular senescence markers.
Nature metabolism · 1 Oct · Koning M, Kovynev A, Fondevila MF et al.
In a phase-2 randomized controlled trial, 31 human participants with fibrotic metabolic dysfunction-associated steatohepatitis (MASH) received either dasatinib plus quercetin or a placebo. Participants took the senolytics or placebo for three consecutive days weekly for three weeks, repeating this schedule over three 7-week cycles.
On paired liver biopsies, 47 percent of participants receiving the senolytics achieved at least a one-stage fibrosis improvement without MASH worsening, compared to 7 percent on placebo. MASH resolved in 53 percent of treated patients versus 7 percent in the placebo group. Senolytic therapy also caused a significantly greater reduction in NAFLD Activity Scores. Single-nucleus RNA sequencing revealed decreased senescence and fibrotic gene signatures alongside fewer fibrogenic cells. While 82 percent of senolytic-treated participants experienced adverse events compared to 43 percent on placebo, all events were self-limiting.
Why it matters
Cellular senescence drives tissue inflammation and fibrosis during aging and chronic disease. This trial provides proof-of-principle evidence in humans that senolytic drugs can reduce senescent cell signatures and reverse organ-level fibrosis.
Caveats
The study was small, evaluating only 31 participants in a proof-of-principle setting. Adverse events were also nearly twice as frequent in the treatment group compared to placebo.
The paper
Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial
Koning M, Kovynev A, Fondevila MF et al.
Nature metabolism
doi.org/10.1038/s42255-026-01643-4