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February 11th

Diabetes Drug Proglitazone Can Stimulate Production of ROS from Mitochonria of WBCs, Meliorating Chronic Granulomatous Disease in Mouse Model

Pioglitazone, a medication approved for treatment of type 2 diabetes, can help bypass genetic defects in chronic granulomatous disease (CJD) to help white blood cells fight bacterial infections, according to researchers at National Jewish Health. Patients with CGD, a rare inherited disorder, lack a functional enzyme, known as NADPH oxidase, which impairs their ability to produce a variety of oxidant molecules, known as reactive oxygen species (ROS), in response to bacterial infection. Normally, ROS destroy bacteria by chemically reacting with their cell walls and other components. As a result of genetic mutation, CGD patients lack this early immune response and suffer ongoing and severe infections, especially of the lungs, liver, skin, and lymph nodes. Pioglitazone, an agonist of the signaling molecule PPAR-gamma, has broad effects on cellular metabolism, which include mimicry of insulin and anti-inflammatory activities. The medication is approved for treatment of type 2 diabetes and is being investigated for use in a variety of other disorders, primarily for its anti-inflammatory properties. Recent findings have suggested that it may also boost the production of ROS. National Jewish Health Professor of Pediatrics, Donna Bratton, M.D., and her colleagues reported in the February 2015 Journal of Allergy and Clinical Immunology that pioglitazone does indeed boost production of ROS in white blood cells by about 30 percent in a mouse model of CGD and in white blood cells from CGD patients. They also found that pioglitazone enhanced the ability of the cells from the CGD mouse model to kill Staphylococcus aureus and Burkholdia cepacia, two pathogens that are difficult to treat and common in CGD.