Fourteen people with a lung disease that has no cure walked into a small study, took two drugs for three weeks, and walked a little farther afterward. That modest result, from a pilot published in 2019, is still the most-cited proof that clearing worn-out cells from the body might help real patients.
The disease is idiopathic pulmonary fibrosis, a progressive and fatal scarring of the lungs. The cells in question are senescent cells, which stop dividing but refuse to go away. Instead they pump out inflammatory signals that provoke the immune system, wear down the tissue around them and nudges neighbors to turn senescent too. Their numbers climb with age. Drugs that destroy them selectively are called senolytics.
From mice to a lung clinic
The pairing of dasatinib and quercetin entered the literature as a senolytic in 2015. James Kirkland, who worked on that discovery, was also the first to take the combination into a human trial, according to a recent review in Frontiers in Bioengineering and Biotechnology. The two-center, open-label study gave 14 patients dasatinib at 100 mg a day and quercetin at 1250 mg a day, three days a week for three weeks.
The main goals were practical: would people stay in the study, and would they finish the planned tests? They did. Retention was 100%, and 13 of the 14 completed every assessment. Just one serious adverse event turned up. Most of the other problems were mild to moderate, mainly respiratory symptoms, skin irritation and bruising, and stomach discomfort.
Then the numbers on function. Six-minute walk distance, four-meter gait speed and chair-stand time all improved significantly, and by amounts the authors called clinically meaningful. They were careful about what that proves. With no placebo group, the pilot offers what they described as initial evidence that senolytics may ease physical dysfunction, and they called for larger randomized trials.
A follow-up Kirkland study in people with diabetic nephropathy found that senescent cell markers and levels of the inflammatory secretions fell significantly, the same review notes.
A company’s setback
The clinic has also handed the field a hard lesson. Unity Biotechnology tested UBX0101, a drug injected straight into the knee, against osteoarthritis. The phase 2 trial used a single injection at several doses, with 45 patients in each group, and measured pain on the WOMAC-A scale at 12 weeks. It failed.
An analysis on the Nintil site, written by someone who had hoped for success, found that placebo and drug groups improved by about the same amount. Sham saline injections into a knee, the writer noted, produce a surprisingly strong placebo effect that can last for months. The analysis also suggested that 12 weeks may have been too early to see a difference in osteoarthritis, which hints that the trial design itself could have been at fault.
Nobody should read the failure as a verdict on the whole idea, and nobody should read the lung pilot as a cure. Dozens of other candidate compounds have now been named, though the clinical record is still thin. The next test is bigger, placebo-controlled trials in diseases like pulmonary fibrosis. Anyone considering these drugs on their own should talk to a doctor first.
Sources
- Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study (EBioMedicine abstract via H1 Connect)
- Senolytics: Eliminating Senescent Cells and Alleviating Intervertebral Disc Degeneration (Frontiers in Bioengineering and Biotechnology)
- Why Unity Biotechnology's UBX0101 failed (Nintil)
- Senolytic Treatment with Dasatinib and Quercetin Confirmed to Reduce the Burden of Senescent Cells in Human Patients (Fight Aging!)
