JAN 07, 2019 11:02 AM PST

First-in-Human Trial of Senolytic Drugs

WRITTEN BY: Nouran Amin

According to a study published in the journal EBioMedicine, the very first results on the treatment of a deadly age-related disease in human patients using drugs called senolytics were reported. Senolytics are drugs that target damaged, toxic cells that are technically not dead—these cells are known to be in a ‘senescent’ state.

Image Credit: longevityfacts.com

"Cellular senescence is clearly emerging as a main player in aging," says Nicolas Musi, MD, manuscript co-author and professor of medicine at UT Health San Antonio. "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."

The presence of cellular senescence has been shown to drive multiple age-related diseases, such as idiopathic pulmonary fibrosis (IPF). "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," says Anoop M. Nambiar, M.D., M.S., associate professor of medicine at UT Health San Antonio.

IDF has limited treatment options despite the presence of two currently available U.S. Food and Drug Administration-approved therapies-- prognosis remains poor and is worse than for many common cancers. Other options include a lung transplantation which may be lifesaving, however, it bests serves younger, healthier patients. "There remains a significant unmet need for safer and better treatments for patients with IPF," Dr. Nambiar said.

Learn more about idiopathic pulmonary fibrosis (IPF):

But with the results of the senolytic therapy—promising treatment may be in the near future for IPF patients. "Though small, this pilot study marks a major breakthrough in how we treat age-related diseases such as IPF," explained Jamie Justice, Ph.D., an assistant professor at Wake Forest medical school as well as 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."

Clinical study participants received two senolytic drugs: dasatinib and quercetin (DQ). These drugs are known to be effective in eliminating senescent cells that have originated from different cell types. "This is the same combination of drugs that was shown to improve pathology in animal models of Alzheimer's disease,” says Dr. Musi.

Results showed consistent improvement following the senolytic therapy in the patient’s mobility which was confirmed through the six-minute walk test, timed sitting-to-standing repetitions, and other measures. "No drug therapies, including the available anti-fibrotic drugs, have ever shown to stabilize, let alone improve, an IPF patient's six-minute walk distance," Dr. Nambiar said. "But in this pilot study of DQ, participants' six-minute walk distance improved an average of 21.5 meters.


Source: Science Daily

About the Author
Doctorate (PhD)
Nouran is a scientist, educator, and life-long learner with a passion for making science more communicable. When not busy in the lab isolating blood macrophages, she enjoys writing on various STEM topics.
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