Senolytics, drugs that combat senescent cells, can now move into larger human trials.
These drugs may alleviate the physical dysfunction in idiopathic pulmonary fibrosis (IPF), according to the findings of a first-in-human pilot study. The study authors told Rare Disease Report
® that the major takeaway from their research is that there are now grounds to conduct a larger study and to continue evaluating these potential therapies.
Investigators from the Mayo Clinic in Rochester conducted a small pilot study of 14 stable IPF patients and treated them with dasatinib plus quercetin (DQ)—a leukemia dug and a plant compound—in order to test how feasible treatment with a senolytic intervention would be. The investigators also examined the safety and change in functional and reported health measures.
Senior study author James Kirkland, MD, PhD, explained to Rare Disease Report
® that senescent cells can form at any time of life, though they often increase with aging and accumulate because of damage. Normally, the cells are removed by the immune system, but once the cells overcome a certain threshold, the propagate and begin to cause frailty, age-related diseases, and early death. All of this had been previously demonstrated in mice models with transplanted senescent cells.
In the study, the 14 IPF patients were treated with 9 doses across 3 weeks. The investigators measured gait speed, walking speed in 6 minutes, a chair rise test, and a physical function test. Compared to the baseline measurements, all patients showed improvement. However, the patients’ lung function, frailty levels, and overall health did not change.
There was 1 serious adverse event reported throughout the study, and there were 16 total respiratory symptoms, 14 cases of skin irritation or bruising, and 12 gastrointestinal discomfort cases.
Kirkland stressed that patients who call their physicians asking about these drugs should be warned not to take them right now. The clinical trials involve patients with very serious, life-threatening conditions, he said, and the risk/benefit ratio is acceptable in these cases.
“If, any only if, we find that these sorts of interventions are safe and effective, I think the field will gradually inch towards giving them for less serious age-related diseases as a way to try to alleviate them,” Kirkland said. “Then, if they turn out to have reasonable side effect profiles or no side effects, the use of them may—over the years—eventually be in a sort of preventive mode for people who aren’t yet sick. But the process has to be gradual.
“These patients calling up asking about getting these drugs should be warned that we don’t know what the side effects are yet of giving these agents these particular ways,” he added. “And that clinical trials are going on and we’ll know sooner or later if these kinds of interventions are safe. But we don’t know now.”
National Institutes of Health director Francis Collins, MD, PhD, wrote in his “Director’s Blog
” that the latest senescent cell research indicates “we’ll be hearing a lot more about senolytics in the years ahead.”
“More preclinical study is needed to understand more precisely how the treatment works,” said Collins, who was not involved in the study. “But, it’s worth noting that clinical trials testing a variety of senolytic drugs are already underway for many conditions associated with senescent cells, including chronic kidney disease, frailty, and premature aging associated with bone marrow transplant.”
The paper, titled “Senolytics in idiopathic pulmonary fibrosis: Results from a first-in-human, open-label, pilot study
,” was published in the journal EBioMedicine