Senolytic Drug Combination Improves Fatty Liver Inflammation Fibrosis in 47% vs 7%: A Small 31-Patient Trial
The senescent cell-clearing drugs dasatinib plus quercetin showed a higher fibrosis improvement rate than placebo in MASH patients with fibrosis.
A combination of senolytic drugs that selectively remove senescent cells showed a signal of histological improvement in human liver disease. Researchers at Amsterdam University Medical Centers in the Netherlands published in Nature Metabolism the results of a phase 2 proof-of-concept randomised controlled trial in 31 patients with metabolic dysfunction-associated steatohepatitis (MASH).
Three intermittent dosing cycles, assessed by liver biopsy
Participants were MASH patients with fibrosis, with a median age of 56, 76% men and 58% with type 2 diabetes. They took dasatinib 100 mg and quercetin 1,000 mg, or placebo, for 3 consecutive days a week for 3 weeks, in a 7-week cycle repeated three times. Comparing liver biopsies before and after treatment, the proportion whose fibrosis improved by one stage or more without worsening of MASH was 47% in the treatment group and 7% in the placebo group. MASH resolution also differed, at 53% versus 7%, and single-nucleus RNA sequencing showed reduced signals of senescence- and fibrosis-related genes.
The researchers reported that adverse events were more frequent in the treatment group, 82% versus 43% in the placebo group, but all resolved on their own. The significance of this study is that it directly tested in people the hypothesis that accumulation of senescent cells contributes to the progression of chronic disease.
However, with only 31 participants and a short treatment period of about 21 weeks, the durability and safety of the effect need to be confirmed in larger follow-up trials. Some authors disclosed financial interests in senolytic-related patents.
- 31 MASH patients with fibrosis, a double-blind, placebo-controlled phase 2 proof-of-concept trial (NCT05506488)
- Primary endpoint (fibrosis improvement of one stage or more without MASH worsening) met in 47% vs 7%; MASH resolution 53% vs 7%
- Adverse events were more frequent at 82% in the treatment group vs 43% with placebo, but all resolved on their own
Limitations A small, short trial of 31 people over about 21 weeks, so a treatment effect cannot be established, and the long-term safety of senolytics is unconfirmed.
Original research
- Koning M, et al. · Amsterdam UMC. Senolytics dasatinib and quercetin in metabolic dysfunction-associated steatohepatitis: a proof-of-principle randomized, controlled trial. Nature Metabolism. DOI: 10.1038/s42255-026-01643-4
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