A new laboratory study suggests that eliminating “dead” cells in the brain may help alleviate a common form of epilepsy.

In a study published in the journal Annals of Neurology, scientists found that removing damaged but non-dying brain cells in mice with epilepsy improved the animals’ memory and reduced the number of seizures. The research focused on temporal lobe epilepsy (TLE), the most common form of epilepsy worldwide, affecting about 50 million people globally.

According to the authors, the findings could help researchers develop the first disease-modifying drugs for temporal lobe epilepsy—medications that target the underlying causes of the disorder rather than merely treating symptoms, Planet Today reports. Existing anti-seizure drugs reduce the frequency and severity of seizures but do not eliminate their root cause, and patients who do not respond to these medications may require brain surgery or nerve-stimulation devices.

Temporal lobe epilepsy can develop after head trauma or infection, and in rarer cases may have genetic causes. However, the precise link between these factors and seizures and memory loss remains unclear.

Meanwhile, a new idea has emerged regarding the role of so-called “zombified” cells in the development of epilepsy.

When cells are damaged, they often undergo programmed cell death and self-destruct. Some cells, however, instead enter a state known as senescence, in which they stop dividing like healthy cells but refuse to die.

Co-author Patrick Forcelli of Georgetown University said that the impact of these cells has become a hot topic among neuroscientists. “There has been growing recognition recently that cellular senescence may play an important role in a number of brain diseases,” he noted.

His team observed that these zombie cells behave similarly to brain cells at the very onset of a seizure. Both zombie cells and pre-epileptic brain regions develop tissue scarring known as fibrosis. In their new paper, Forcelli and colleagues asked whether removing senescent cells from the brain could alter the symptoms of temporal lobe epilepsy.

The researchers began by looking for signs of senescence in the brains of patients with temporal lobe epilepsy. Some patients with TLE undergo surgical removal of part of the brain to reduce or eliminate seizures. The scientists compared brain tissue samples from these patients with samples obtained at autopsy from people without TLE.

Notably, the group without temporal lobe epilepsy was significantly older than the epilepsy group, Forcelli said. Despite this, tissue samples from the epilepsy group contained, on average, five times more senescent cells.

Next, in mouse models of temporal lobe epilepsy, the team showed that the animals also exhibited more signs of senescence in the brain than mice without seizures. These signs were most closely associated with microglia—cells that are part of the brain’s own immune system. Dysfunctional microglia are increasingly linked to brain disorders, including dementia.

The team then attempted to eliminate senescent cells in the mice. Some animals were given a combination of a leukemia drug and an anti-inflammatory plant pigment. Previous studies have repeatedly shown that this unusual cocktail reduces the number of senescent cells; such treatments are known as senolytics.

James Kirkland, a gerontologist at the Cedars-Sinai Medical Center who first identified the senolytic effects of these two compounds, explained that they target mechanisms senescent cells use to resist normal cell death.

The dual treatment improved several symptoms in the mice. “We were able to normalize memory function in the mice,” and significantly reduce the number of seizures, Forcelli said. “We also protected a large proportion of animals from developing seizures, so in that respect this is a disease-modifying approach.”

In a separate experiment, Forcelli’s team attempted to remove all microglial cells—both healthy and senescent—from mice with temporal lobe epilepsy. This broad removal did not help the animals, in part because the senescent cells proved resistant to the wide-spectrum treatment.

“We eliminated a huge number of healthy microglial cells but left only the senescent ones,” Forcelli said. Previous studies have shown that microglia play both damaging and protective roles in epilepsy, he added. The influence of a small population of senescent cells opposing a larger population of healthy microglia may explain this discrepancy. It also suggests that any therapy targeting microglia must precisely target the senescent cells.

Forcelli plans further studies to determine the optimal timing for administering potential senolytic drugs in temporal lobe epilepsy. For example, should treatment be given immediately after a traumatic brain injury, or could it remain effective if administered a week or even a month later?

Kirkland also noted that targeting senescence and related processes could have applications in many different diseases. However, he cautioned the general public to wait for the results of formal clinical trials rather than taking commercially available supplements claiming senolytic properties.

Such supplements may contain ingredients not listed on their labels or dangerously high concentrations of active substances, he warned.

“The problem with quality control is the lack of regulation,” Kirkland said. In the United States, dietary supplements do not undergo the same rigorous testing for safety, efficacy, and quality as pharmaceutical drugs, so claims about their effects on the body are often unverified or insufficiently tested.

Encouragingly, rigorous clinical trials of various types of senolytics are now underway. Kirkland said that preclinical research has identified around 60 to 70 diseases in which senolytics may slow or prevent disease progression. “A whole new world is emerging,” he concluded.