The combination of dasatinib and quercetin as senolytic medications in idiopathic pulmonary fibrosis (IPF) is feasible and generally well tolerated, according to a study published in eBioMedicine.
The 2 most commonly prescribed medications in IPF are the antifibrotics nintedanib and pirfenidone, which slow disease progression but are not curative. Scientists have discovered that IPF pathophysiology is driven in part by cellular senescence and that this may be a promising therapeutic target.
Senolytics are a class of drugs that work by inhibiting senescent cell anti-apoptotic pathways. Studies investigating the merits of the senolytics dasatinib and quercetin reveal that they work synergistically and improve clinical function when used intermittently in the presence of bleomycin-induced lung injury.
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The authors of this study sought to investigate the feasibility and tolerability of both drugs to facilitate larger trials studying their efficacy in IPF. They recruited eligible participants (n=12) from the University of Texas Health San Antonio IPF clinic between December 2018 and May 2019. Recruited participants must have had a confirmed diagnosis of IPF and demonstrated stable disease (defined as ≤2 acute exacerbations of IPF in the preceding year); they also must have been on stable antifibrotic medications for the last 3 months.
Read more about IPF epidemiology
Participants were randomized to either the treatment group or the control. Participants in the treatment group were required to self-administer the combination of dasatinib and quercetin intermittently at 100 mg orally per day; they took the drugs for 3 consecutive days in 3 consecutive weeks (9 doses in total). Participants in both groups continued to receive pirfenidone throughout the study.
The research team monitored reported adverse events. They found that participants in the treatment group experienced an approximate 3-fold increase in nonsevere adverse effects—but none that required premature termination. Overall, they found that the combination of the 2 senolytic drugs were feasible and generally well tolerated.
“These data will aid in the study design of future larger prospective [randomized controlled trials] of [dasatinib plus quercetin] in patients with IPF,” the authors of the study concluded.
Reference
Nambiar A, Kellogg III D, Justice J, et al. Senolytics dasatinib and quercetin in idiopathic pulmonary fibrosis: results of a phase I, single-blind, single-center, randomized, placebo-controlled pilot trial on feasibility and tolerability. EBioMedicine. 2023;90:104481. doi:10.1016/j.ebiom.2023.104481
