Researchers at Mayo Clinic have reported that a combination of the cancer drug dasatanib and the supplement quercetin can reduce the negative effects of senescent cells in diabetic kidney disease. Their findings were published in eBioMedicine, a journal from The Lancet.
Diabetic kidney disease is a major health issue in the United States, affecting over 12 million people and representing the primary cause of kidney failure. While current treatments can slow down the decline in kidney function, there is no cure for this condition.
Senescent cells, sometimes called "zombie cells," are cells that do not die as they should and remain in tissues, contributing to aging and disease progression. Scientists have been exploring senolytics—substances that target these lingering cells—as a possible way to protect organs such as the kidneys.
In earlier research, Dr. Hickson and other Mayo Clinic scientists found that dasatanib combined with quercetin reduced senescent cells in skin and fat tissue among patients with diabetic kidney disease. However, its impact on the kidneys themselves had not been previously described.
"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, M.D., Ph.D., nephrologist and lead author of the study who conducted this work during her postdoctoral fellowship at Mayo Clinic.
Using a preclinical model of diabetic kidney disease, researchers observed improvements in kidney function and protective factors after administering the combination therapy. They also noted reductions in injury markers, senescent cell presence, and inflammation. In laboratory studies with human kidney cells, similar decreases were seen in both senescent cell numbers and related inflammatory processes.
"The results show this combination treatment holds potential to help reduce and halt kidney damage from diabetes," said Dr. Hickson. "Promising findings from these two investigations now suggest that larger scale studies using senolytics should be pursued in patients to improve kidney health."
