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Miller School Researchers Link Lipid Accumulation to Diabetic Kidney Disease

A study led by a Miller School doctoral student has linked intracellular lipid accumulation to cellular dysfunction in diabetic kidney disease, the ninth-leading cause of death in the world.

From left, G. Michelle Ducasa, Ph.D., with Alessia Fornoni, M.D., Ph.D., when Ducasa received her doctorate.
From left, G. Michelle Ducasa, Ph.D., with Alessia Fornoni, M.D., Ph.D., when Ducasa received her doctorate.

G. Michelle Ducasa, who recently received her Ph.D. degree in the Miller School’s Molecular and Cellular Pharmacology program, carried out the groundbreaking research, which was published as the cover article in the Journal of Clinical Investigation.

“Our study identified a potential new treatment strategy for diabetic kidney disease,” said Alessia Fornoni, M.D., Ph.D., professor of medicine, chief of the Katz Family Division of Nephrology and Hypertension, and director of the Peggy and Harold Katz Family Drug Discovery Center. She mentored Dr. Ducasa, together with Flavia Fontanesi, Ph.D. and Sandra Merscher, Ph.D., toward the completion of interdisciplinary study.

“By targeting the accumulation of peroxidized cardiolipin and esterified cholesterol, we can improve the functioning of mitochondria in podocytes, the key cells responsible for the filtration barrier in the kidneys,” Dr. Fornoni said. “Our next step is to validate this approach using compounds that are now ready for phase II-III clinical trials for the treatment of kidney diseases.”

Miller School co-authors of the study, “ATP-Binding Cassette A1 Deficiency Causes Cardiolipin Driven Mitochondrial Dysfunction in Podocytes,” were Santanu Banerjee, Ph.D., and Armando Mendez, Ph.D., as well as Drs. Ducasa, Fornoni, Fontanesi and Merscher. Other co-authors in the international collaborative study included Reiko Inagi Ph.D., and Yu Ishimoto, M.D., Ph.D., of the University of Tokyo, and Hazel H. Szeto, M.D., Ph.D., at the Social Profit Network Research Lab in New York.

In her laboratory research, Dr. Fornoni has played a leading role in describing “fatty kidney disease,” a disorder where lipid droplets accumulate in the kidney cells in chronic kidney disease of both metabolic and non-metabolic origin.

“Our new study describes the ‘cross talk’ between the lipid droplets and the mitochondria, creating an impairment that leads to inefficient respiration of the cells,” she said. “Targeting this pathway might prove to be efficacious for the treatment of chronic kidney disease.”

Currently there are no definitive treatments for diabetic kidney disease. Strict control of the patient’s glucose and blood pressure can slow the disease progression, but do not revert or treat it, Dr. Fornoni said.

“We are hopeful that the study led by Dr. Ducasa will point the way to new treatments for this life-threatening condition,” she said.


Tags: diabetic kidney disease, lipid accumulation