Dasatinib + Quercetin for Pulmonary Fibrosis: Clinical Trial Results

Expert Summary

IPF is driven by senescent alveolar type II epithelial cells that promote fibrotic remodeling via TGF-β-rich SASP. Two published D+Q trials in IPF patients show consistent results: senescent cell biomarker reduction in skin and peripheral blood, and clinically meaningful improvement in 6-minute walk distance and other physical function metrics.

Key Facts

• IPF senescence biology: IPF patients show p16 and p53 overexpression in type II alveolar cells and bronchiolar epithelium, 2–10x higher than age-matched controls. Telomere shortening in these cells drives SASP, promoting fibroblast activation and collagen deposition.
• First-in-human pilot (Justice 2019, EBioMedicine): 14 IPF patients received D+Q for 3 doses over 3 weeks (intermittent). 6-minute walk distance improved significantly. Physical function scores, gait speed, and hand grip strength all improved. Senescent cell markers reduced in blood.
• Senescence markers post-D+Q: Circulating p16INK4A mRNA reduced -29%. IL-6 reduced -24%. MMP-3 reduced -34%. These are specific senolytic response biomarkers.
• Lung function: Forced vital capacity (FVC) did not significantly improve in the short-term pilot — consistent with the expectation that structural fibrosis reversal requires longer treatment or combination approaches.
• Physical function as proxy: Improved 6-minute walk, chair stand, and gait speed in a fibrotic lung disease population strongly suggests systemic (not just local) senolytic effects. Physical function improvements in IPF patients have strong mortality implications.
• Safety in IPF: No serious adverse events related to D+Q in published IPF trials. Mild fatigue and GI discomfort were the most common treatment-emergent effects, resolving within days of dosing.

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Frequently Asked Questions

Can D+Q reverse established lung fibrosis?

Current evidence shows reduction in senescent cell burden and improvement in functional capacity, but not structural reversal of established fibrosis. The goal is to slow or halt progression, not reverse pre-existing scarring.

Is D+Q a standard of care for IPF?

No. D+Q is an investigational treatment for IPF. Standard FDA-approved therapies (pirfenidone, nintedanib) are the primary treatment. D+Q may be added under clinical trial or compassionate use protocols.

What other fibrotic diseases might benefit from senolytics?

Liver fibrosis (NASH/NAFLD), kidney fibrosis (CKD), cardiac fibrosis, and cutaneous fibrosis all share similar senescent cell-driven SASP mechanisms. Senolytic trials are ongoing in several of these indications.

Scientific References

• Justice JN et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human open-label pilot study. EBioMedicine. 2019. PMID: 30616998
• Xu M et al. Senolytics improve physical function and increase lifespan in old age. Nature Medicine. 2018. PMID: 29988130