New peptide halts diabetic nephropathy in mice

Investigators in Spain have shown that a peptide can counteract diabetic nephropathy in mice by jamming JAK/STAT signaling. This countermeasure reduced renal inflammation and fibrosis, and improved renal function and albuminuria, according to their study published September 8, 2016 in the Journal of the American Society of Nephrology.

“This is the first evidence of a successful and safe peptide-based approach for the specific inhibition of JAK/STAT-mediated responses in diabetic nephropathy,” the authors wrote.

The JAK/STAT signaling pathway is the mediator through which hyperglycemia and inflammation contribute to chronic and acute kidney diseases. For this study, the investigators targeted a protein, called Suppressor Of Cytokine Signaling 1 (SOCS1), which helps regulate JAK/STAT. Accordingly, they developed a cell-permeable peptide that mimics the activity of SOCS1.

When the researchers tested the peptide in a mouse model of diabetic nephropathy, they found that it inhibited JAK/STAT activation in the kidneys of the mice. This effect increased the urine albumin-to-creatinine ratio, reduced renal fibrosis between 44% and 38%, and decreased inflammatory markers by about 50%. These effects occurred independently of changes in glycemic and lipid levels.

The investigators then tested the peptide with in vitro experiments of diabetic mouse cells, which confirmed the in vivo findings.

“In conclusion, our study identifies SOCS1 mimicking as a feasible therapeutic strategy to halt the onset and progression of renal inflammation and fibrosis in diabetic kidney disease,” the authors wrote.

“Our goal is to develop the compound as a novel approach to combat chronic complications of diabetes,” said co-lead investigator Carmen Gomez-Guerrero, PhD, researcher in the Nephrology Group at Fundacion Jimenez Diaz University Hospital and Professor at the Universidad Autónoma de Madrid, in Madrid, Spain. “We plan to initiate preclinical development to support early-phase clinical trials.”

Fundacion Jimenez Diaz University Hospital and the Universidad Autónoma de Madrid have applied for a patent for the peptide, with Dr. Gomez-Guerrero and co-lead investigator Jesus Egido, MD, PhD, named as inventors.