SAN ANTONIO, Texas — It’s been given a scary name and it’s making a scary disease even more of a concern for sufferers. What doctors refer to as “zombie cells,” which develop from cellular stress that’s long known to be involved in the development of cancer and aging, have been implicated in Alzheimer’s disease for the first time.
The new findings could lead to new treatments that could potentially slow, if not stop the disease altogether.
Researchers at the University of Texas Health Science Center at San Antonio found this cellular stress, called cellular senescence, partially causes harmful tau proteins that are known to be a marker of 20 human brain diseases, such as Alzheimer’s and traumatic brain injury. Cellular senescence keeps a cell alive, but functioning abnormally and secreting substances that kill adjacent cells, like a zombie.
“When cells enter this stage, they change their genetic programming and become pro-inflammatory and toxic,” explains study senior author Dr. Miranda E. Orr, instructor of pharmacology at UT Health San Antonio, in a release. “Their existence means the death of surrounding tissue.”
The researchers examined postmortem brain tissue from Alzheimer’s patients and identified senescent cells. They also found the so-called zombie cells in postmortem tissue from sufferers of another brain disease called progressive supranuclear palsy.
So doctors sought to learn what would happen should the zombie cells be removed from the brains of mice likely to be suffering from Alzheimer’s-like ailments. Researchers found four types of mice that model Alzheimer’s disease, then used a combination of drugs to clear senescent cells from the brains of the mice.
After three months, the researchers were encouraged by their findings.
“The mice were 20 months old and had advanced brain disease when we started the therapy,” says Dr. Orr. “After clearing the senescent cells, we saw improvements in brain structure and function. This was observed on brain MRI studies (magnetic resonance imaging) and postmortem histology studies of cell structure. The treatment seems to have stopped the disease in its tracks.”
The drug combination used by the researchers included dasatinib, a chemotherapy medication approved by the U.S. Food and Drug Administration to treat leukemia; and quercetin, a natural flavonoid compound found in fruits, vegetables, and certain beverages such as tea. These drugs used in combination reduced cell senescence and tau tangles that cause Alzheimer’s in mice.
“The fact we were able to treat very old mice and see improvement gives us hope that this treatment might work in human patients even after they exhibit symptoms of a brain disease,” says the study’s first author Dr. Nicolas Musi, professor of medicine and director of the Sam and Ann Barshop Institute at UT Health San Antonio. “This is the first of what we anticipate will be many studies to better understand this process. Because these drugs are approved for other uses in humans, we think a logical next step would be to start pilot studies in people.”
The study was published in the journal Aging Cell.