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Degenerative Changes Identified in Spinal Discs and Reversed With Drug Cocktail In Diabetic Mice
Date:5/17/2013

bination of oral anti-inflammatory drugs and blockers of advanced glycation end products could slow degenerative disc and vertebral changes.

The diabetic mice showed decreased trabecular bone, reduced disc height, and increased disc wedging, a sign of hyperlordosis. “What really surprised us is the effect on the nucleus pulposus, which had focal areas of loose disorganized tissue and cells,” said Dr. Iatridis.

“AGEs accumulate in intervertebral discs as the body ages and contribute to a chronic inflammatory state in degenerated discs,” said Svenja Illien-Jünger, PhD, the study’s lead author, and postdoctoral fellow in the Iatridis Spine Laboratory in the Department of Orthopaedics at the Icahn School of Medicine. “Diabetes is a disease involving accelerated aging and degeneration.” Dr. Illien-Jünger explained that the drugs used in the study are all approved by the FDA: pentosan polysulfate as an anti-inflammatory drug, pyridoxamine for the prevention of AGE formation, and enalapril, an AGE inhibitor and they expected an additive effect.

Researchers compared three groups of age-matched, middle-aged mice: non-diabetic, diabetic, and diabetic mice treated with pentosan polysulfate, pyridoxamine and enaprinil, an angiotensin converting enzyme inhibitor, which is standard treatment for diabetic patients with kidney disease. Mice ingested standard rodent food, known to be an abundant source of AGEs.

The study was funded by the National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health and the Juvenile Diabetes Research Foundation. In addition to Dr. Iatridis and Dr. Illien-Jünger, other Mount Sinai investigators involved in the study include Gary E. Striker, MD, Professor, Geriatrics and Palliative Medicine; Helen Vlassara, MD, Professor, Experimental Diabetes and Aging; Damien M. Laudier, BS , Senior Associate Researcher; and Fabrizio Grosjean, MD, Assistant Professor, Nep
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