Can a new drug combination help fight off the ill effects of cellular aging?
Senolytics are a class of drugs that target cells that have entered senescence, meaning an old age stage that renders them toxic to surrounding, healthy cells.
These drugs aim to attack the harmful cells selectively, and so prevent the development of age-related diseases, or to reduce their impact.
Among other conditions, cell senescence can lead to idiopathic pulmonary fibrosis (IPF), a chronic disease that progressively causes the scarring of lung tissue, and which can be fatal.
Although the Food and Drug Administration (FDA) have already approved two drugs for the treatment of IPF — nintedanib and pirfenidone — the prognosis for people with this condition remains unsatisfactory. Researchers have noted that the median survival rate for IPF is about 3 to 5 years.
"IPF is a devastating and progressive fibrotic lung disease with a median survival of less than 5 years in newly diagnosed adults, usually over 60 years of age," explains Dr. Anoop Nambiar, an associate professor at the University of Texas (UT) Health Science Center at San Antonio, and the founding director of the Interstitial Lung Disease Program at the university.
"There remains a significant, unmet need for safer and better treatments for patients with IPF," he adds.
For this reason, Dr. Nambiar and colleagues from UT Health, and the Mayo Clinic in Rochester, MN, have recently conducted a clinical trial for two other drugs — dasatinib and quercetin — that the FDA have approved for treating conditions other than IPF.
This is the first time researchers have tested the two drugs in human participants with IPF, and the study's findings now appear in the journal EBioMedicine, which is a Lancet publication.
Testing a promising drug combo
In this trial, the research team worked with 14 participants with stable, mild-to-moderate IPF. Each person took dasatinib and quercetin orally for 3 consecutive days per week, and over the course of 3 consecutive weeks.
The investigators performed clinical tests both at baseline and at the end of the study. They asked the participants to fill in questionnaires assessing their symptoms on a weekly basis, and they also evaluated the volunteers' physical functioning. Moreover, the researchers looked at the safety and tolerability of the two drugs.
Dr. Nambiar and colleagues found that the drugs chiefly improved the participants' mobility, which IPF significantly impairs in people with the condition. Most of the participants experienced more than 5 percent improvement in markers of mobility.
"No drug therapies, including the available anti-fibrotic drugs, have ever shown to stabilize, let alone improve, an IPF patient's 6-minute walk distance," notes Dr. Nambiar.
"But in this pilot study [...] participants' 6-minute walk distance improved an average of 21.5 meters," he adds.
Though the researcher warns that "[w]e should be cautious about whether this finding is true based upon this small study without a placebo control group," he argues that "this and other results warrant further study in larger randomized, controlled trials."
Attacking 'a main player in aging'
As for side effects, the participants most frequently reported respiratory problems — including coughing and shortness of breath — as well as heartburn. However, all of these symptoms were mild to moderate, and did not require the volunteers to abandon the trial.
So, although the current study was small and lacked a control group, the researchers are confident that they are on the right path toward finding a better treatment for age-related conditions.
"This is the same combination of drugs that was shown to improve pathology in animal models of Alzheimer's disease, which our group, including Dr. Miranda Orr at UT Health San Antonio, demonstrated 3 months ago for the first time," says co-author Dr. Nicolas Musi.
"Cellular senescence is clearly emerging as a main player in aging. Previously, no published data existed to demonstrate that drugs targeting cellular senescence could be safely given to older patients, or that they might be used to treat diseases of aging such as IPF. The pilot research we've reported is preliminary but encouraging."
Dr. Nicolas Musi