A small first-in-human trial of a medicine that is a potential game changer in the treatment of age-related diseases like Alzheimer's has shown promise in San Antonio.
UT Health San Antonio researchers, collaborating with researchers at the Mayo Clinic and the Wake Forest School of Medicine, wanted to see if a particular combination of medicines called senolytics were safe for humans to take.
UT Health San Antonio's Interstitial Lung Disease Program Director Dr. Anoop Nambiar said senolytics target a certain type of cell that we get more of as we age. They're senescent cells.
"(Senescent cells) basically are these zombie-like cells that are dysfunctional — they don't work properly — but at the same time, they don't die. They create a toxic environment so other cells and other tissues don't work properly," Nambiar said.
The toxic environment created by these zombie cells is implicated in a number of age-related diseases, including Alzheimer's, Parkinson's, and idiopathic pulmonary fibrosis — a scarring of the lungs that is often-times fatal.
“Normal lungs should be very compliant and soft, and a fibrotic lung usually has a lot of stiffness — it’s very hard; it’s like a brick. And it’s hard for oxygen to get in and out of the lungs and carbon dioxide to get out,” Nambiar said.
The prognosis for people with IPF is grim. Many die within five years. So when testing the safety of this medication, Nambiar said they asked people with that illness if they'd like to join the trial.
“We picked IPF as a prototypical disease associated with aging,” Nambiar said. “But also because it’s such a devastating disease, and so there’s really a significant unmet need for better treatments and more effective, safer treatments for IPF patients.”
Twelve IPF patients participated. Over the six week trial, each participant received two senolytic drugs: dasatinib and quercetin. They took it for three consecutive days each week for three consecutive weeks
Researchers simply wanted to figure out if the medicine was safe for humans to take, but Nambier said his IPF patients, whose physical activity was limited by their scarred lungs before the trial, got something unexpected.
"Patients were able to walk farther in this very short, intermittent dosing schedule, and also function better," Nambiar said.
According to Nambiar, the majority of patients exhibited mobility gains of greater than 5 percent, though their pulmonary function did not change.
The idea that doctors might someday be able to treat age-related diseases by targeting cellular senescence is an encouraging one, said Dr. Nicolas Musi, director of the UT Health San Antonio’s Sam and Ann Barshop Institute for Longevity and Aging Studies. He and Nambiar co-authored the manuscript on this research trial.
“Cellular senescence is clearly emerging as a main player in aging,” Musi said. “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.”
Now that preliminary research has suggested this medicine — at least in the short term — is safe for humans, there will be further study and larger trials.
Nambiar is currently enrolling patients in a larger study of this medication’s safety and effectiveness in IPF patients at UT Health San Antonio and the South Texas Veterans Health Care System.
Bonnie Petrie can be reached at bonnie@tpr.org or on Twitter @kbonniepetrie
