Study will evaluate senolytics — drugs that clear defective ‘zombie’ cells
A clinical trial conducted at UT Health San Antonio aims to “stomp” out Alzheimer’s disease. Clearing old, damaged “zombie” cells from the brain may be one way to do it.
The study, called SToMP-AD (Senolytic Therapy to Modulate the Progression of Alzheimer’s Disease), seeks 21 San Antonio-area volunteers to participate. Individuals must be 60 or older and have a legally authorized representative to accompany them at study visits. Participants will have a diagnosis of mild cognitive impairment or early Alzheimer’s disease and elevated levels of a protein called tau in cerebrospinal fluid.
SToMP-AD is offered by the Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, a national center of excellence at UT Health San Antonio. The Biggs Institute, in collaboration with UT Rio Grande Valley, is one of 33 centers in the nation and the only one in Texas recognized as a National Institute on Aging-Designated Alzheimer’s Disease Research Center (ADRC).
Families and individuals interested in SToMP-AD eligibility are invited to contact Rose Ann Barajas of the Biggs Institute at 210-450-8219 or Barajasr@uthscsa.edu.
SToMP-AD will evaluate the potential of medications called senolytics to treat the memory-robbing disease.
Senolytics clear senescent cells. These are cells that have become old or damaged. Like zombies, they do not die. Instead, they spew out toxic substances that harm other cells.
“This research has been developed from the ground up at UT Health San Antonio,” said Mitzi Gonzales, PhD, assistant professor of neurology and Biggs Institute investigator who leads the SToMP-AD study in San Antonio. “Dr. Miranda Orr, now with Wake Forest University, and others at our institution produced a seminal paper that for the first time linked cellular senescence with tau aggregation in the brain and in animal models. In collaboration with Dr. Orr and Wake Forest, we are the first to run a clinical trial to evaluate senolytics therapy for treatment of Alzheimer’s disease.”
SToMP-AD explores whether delivering two medications together — dasatinib and quercetin — can reduce senescent cell numbers and tau aggregates in the brain. The team also will, at set intervals, evaluate participants on dementia and Alzheimer’s disease scales that assess memory, attention, reasoning and many other aspects of cognition.
Both dasatinib and quercetin are utilized today in other conditions. The U.S. Food and Drug Administration approved dasatinib for treating certain types of leukemia. Quercetin, a plant pigment naturally found in green tea and other foods, is not approved as a therapeutic but the FDA conferred “generally recognized as safe” status on it.
“This combo, called DQ, has been studied for a few years, but not in this at-risk, geriatric population,” Gonzales said. “These drugs have proven to be safe in other settings, but even so, we are doing many safety checks in SToMP-AD. Out of an abundance of caution, we will have people come to the clinic every two weeks for the first three months of the trial.”
The team completed a small study of DQ administration in five participants and presented the results in December 2022 at the Clinical Trials on Alzheimer’s Disease conference in San Francisco. Safety in these participants was confirmed. Minor adverse effects included urinary tract infections and gastrointestinal distress.
“The treatment was very well-tolerated, we had no premature discontinuation among the participants, and we saw trends that are in the right direction,” Gonzales said. “We did not have a control group, which is needed in clinical research studies to confirm findings, but we were encouraged by our preliminary data.