A cancer drug paired with a plant supplement clears 'zombie cells' from diabetic kidneys

Published in eBioMedicine (The Lancet). Mayo Clinic.

Senescent cells are supposed to die. That is the deal: a cell sustains damage, stops dividing, and is cleared away by the immune system. But in chronic diseases like diabetes, the cleanup crew falls behind. Damaged cells linger in tissues, refusing to die but no longer functioning properly. They pump out inflammatory signals that damage their neighbors. Researchers have taken to calling them "zombie cells," and in the kidneys of people with diabetes, they accumulate in ways that accelerate organ decline.

Now, a team at Mayo Clinic has shown that a short course of two drugs, the cancer therapy dasatinib and the plant-derived supplement quercetin, can reduce these zombie cells in a preclinical model of diabetic kidney disease, improving kidney function and dialing down inflammation. The findings were published in eBioMedicine, a Lancet publication.

Before treatment: lingering cells and rising damage

Diabetic kidney disease affects more than 12 million people in the United States and remains the leading cause of kidney failure. Newer treatments can slow the decline, but there is no cure. The progressive nature of the disease is driven in part by the accumulation of senescent cells, which release a cocktail of inflammatory molecules known as the senescence-associated secretory phenotype, or SASP. These signals recruit more immune cells, promote fibrosis, and erode the kidney's filtering capacity.

After treatment: fewer zombie cells, better function

The approach the Mayo team used is called senolytic therapy, a strategy that selectively targets and eliminates senescent cells. In a preclinical model of diabetic kidney disease, the combination of dasatinib and quercetin achieved several things simultaneously: it reduced the abundance of senescent cells, decreased the inflammatory signals those cells produce, boosted protective factors in the kidney, and improved overall kidney function.

The results were reinforced by experiments in cultured human kidney cells, where the same drug combination reduced both the number of senescent cells and the inflammatory cascade they trigger.

"Our study found that the combination therapy, given over a short period of time, reduced the abundance of senescent cells in a preclinical model of diabetic kidney disease and also improved kidney function," said LaTonya Hickson, MD, a nephrologist at Mayo Clinic in Florida and the study's principal investigator.

Building on earlier human evidence

This is not the first time Mayo Clinic has tested the dasatinib-quercetin combination in the context of diabetic kidney disease. In a previously conducted pilot clinical trial, Hickson and colleagues demonstrated that the combination reduced senescent cells in skin and fat tissues of patients with diabetic kidney disease. What had not been established was whether the therapy also affected senescent cells and protective factors specifically within the kidney itself.

"It was important to prove that this one-time, short-course treatment has an effect on the kidneys, and we wanted to do so without invasive procedures in patients," said Xiaohui Bian, MD, PhD, a nephrologist who conducted the work as a postdoctoral fellow at Mayo Clinic and is the study's lead author.

From preclinical model to the next clinical step

The study has clear limitations. The preclinical model, while useful for establishing biological plausibility, does not replicate the full complexity of human diabetic kidney disease. The kidney is a structurally intricate organ with dozens of cell types, and how senolytic therapy interacts with that complexity in living patients over extended periods is not yet known. The pilot trial showed effects on skin and fat, but direct evidence of kidney senescent cell clearance in humans has not been demonstrated.

Dasatinib is an approved cancer drug with a known side effect profile, including risks of fluid retention and bleeding. Quercetin is a widely available supplement found in foods like onions and apples, though its bioavailability when taken orally is limited. Whether the combination can be given safely and repeatedly to the predominantly older population with diabetic kidney disease, many of whom take multiple other medications, remains to be studied in larger trials.

"The results show this combination treatment holds potential to help reduce and halt kidney damage from diabetes," Hickson said. "Promising findings from these two investigations now suggest that larger scale studies using senolytics should be pursued in patients to improve kidney health."

The concept is appealing: a short course of treatment that clears out dysfunctional cells and resets the inflammatory environment. Whether that concept holds up in the controlled setting of a large clinical trial is the question that matters next.