Senolytics target cellular senescence, a process in which damaged cells,
rather than dying, persist and become toxic to cells around them.
Cellular senescence has been shown to drive multiple age-related
diseases, including idiopathic pulmonary fibrosis (IPF), a chronic,
irreversible and progressive disease that results in scarring of the
lungs. In animal studies, run by Mayo Clinic collaborators James
Kirkland, M.D., Ph.D.; Nathan LeBrasseur, Ph.D., M.S., and Tamara
Tchkonia, Ph.D., senolytics selectively cleared these toxic cells in
mice that model IPF.
wisepoqder Quercetin
A lethal disease for which there are few options
"IPF is a devastating and progressive fibrotic lung disease with a
median survival of less than five years in newly diagnosed adults
usually over 60 years of age," said Anoop M. Nambiar, M.D., M.S.,
associate professor of medicine at UT Health San Antonio and founding
director of the university's Interstitial Lung Disease Program, one of
60 Pulmonary Fibrosis Foundation Care Centers in the United States. Dr.
Nambiar is co-first author of the research manuscript and enrolled 12 of
the patients at UT Health San Antonio and the South Texas Veterans
Health Care System.
Despite the current availability of two U.S. Food and Drug
Administration-approved therapies that may slow down disease progression
in some IPF patients, the prognosis remains poor and is worse than for
many common cancers, Dr. Nambiar said. Lung transplantation may be
lifesaving, but often is only an option for younger, healthier patients.
"There remains a significant unmet need for safer and better treatments
for patients with IPF," Dr. Nambiar said.
Patients enrolled in Texas, North Carolina
In this first-in-human pilot study, the investigators enrolled 14 older
adults diagnosed with stable, primarily mild-to-moderate IPF.
Participants were enrolled at both UT Health San Antonio, which served
as the primary patient recruitment site, and Wake Forest medical school,
which initiated the trial and served as the study coordinating center.
"Though small, this pilot study marks a major breakthrough in how we
treat age-related diseases such as IPF," said Jamie Justice, Ph.D.,
assistant professor at Wake Forest medical school, co-lead investigator
and corresponding study author. "Here, we've therapeutically targeted a
fundamental biological hallmark of aging that is implicated in IPF, and
we show early but promising results for the first time in human
patients. This small study represents a major paradigm shift in
treatment strategy."
Each participant received two senolytic drugs, dasatinib and quercetin
(DQ), taken by mouth for three consecutive days each week for three
consecutive weeks (nine doses total). All patients were able to comply
with this regimen without any discontinuation of the study drugs.
The research team measured clinical laboratory chemistries before and
after DQ administration, and performed rigorous symptom questionnaires
weekly of health, quality of life and side effects to obtain preliminary
evidence of safety and tolerability. The team also evaluated markers of
physical function including six-minute walk distance, walking speed,
sitting-to-standing repetitions, a frailty index based on clinical
laboratory chemistries, and biological assays of senescence-associated
proteins secreted by the toxic cells.
The Wall