JACKSONVILLE, Fla. - Mayo Clinic researchers have identified a drug-and-supplement combination therapy that is capable of reducing the harmful effects of senescent cells - also known as "zombie cells" - in diabetic kidney disease. In eBioMedicine, a publication of The Lancet, the team reported that the combination of the cancer drug dasatanib and a naturally occurring substance known as quercetin decreased inflammation and boosted protective factors in the kidney.
Diabetic kidney disease affects more than 12 million people in the U.S. and is the leading cause of kidney failure. While newer treatments can delay loss of kidney function, there is currently no cure.
"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," says LaTonya Hickson, M.D., a nephrologist at Mayo Clinic in Florida and principal investigator of the study.
To extend the health of the kidney, researchers have been interested in addressing the presence of senescent cells, which fail to undergo the natural death process and linger in tissues, contributing to aging and disease. The treatment approach involves senolytics, natural and designed substances that together selectively target senescent cells.
In a previously conducted, pilot clinical trial, Dr. Hickson and Mayo Clinic researchers found that the combination of dasatanib and quercetin reduced senescent cells in skin and fat tissues in patients with diabetic kidney disease. However, the effect of the combination therapy on senescence and protective factors in the diabetic kidney had not yet been 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," says Xiaohui Bian, M.D., Ph.D., a nephrologist who conducted the work as a postdoctoral fellow at Mayo Clinic and is lead author on the study.
In a preclinical model of diabetic kidney disease, the team found that the combination therapy improved kidney function and protective factors while reducing injury, senescent cells, and inflammation. In cultured human kidney cells, the combination therapy also reduced the abundance of senescent cells and the inflammatory process they prompt.
"The results show this combination treatment holds potential to help reduce and halt kidney damage from diabetes," says 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."
Review the study for a complete list of authors, disclosures and funding.
