Scientists have known for a long time that skin and blood cells obtained from A-T patients do not survive as well as cells from healthy people, and recent discoveries have hinted that A-T cells, especially brain cells in A-T patients, may be dying because of defective cell metabolism. The A-T Children’s Project has therefore funded Rodney Shackelford, PhD from the LSU Health Sciences Center in Shreveport, Louisiana to determine if the correction of abnormal metabolism in A-T cells, specifically abnormal nicotinamide adenine dinucleotide (NAD) metabolism, increases their survival in culture.
NAD, a form of Niacin or vitamin B3, is necessary for energy production and communication within cells. Previously, Dr Shackelford and others have shown that NAD levels are low in cells obtained from patients with A-T and in the brains of A-T mice. More recently, Dr. Shackelford has observed that levels of the protein responsible for making NAD in cells, named Nampt, are also low in human A-T autopsy brain samples and cultured patient derived cells.
Dr. Shackelford believes that increasing NAD levels in A-T cells without depending on Nampt might improve their rate of survival. Two cellular metabolites can do just this: nicotinic acid and nicotinamide riboside. Both are nutritional supplements, but nicotinic acid can produce significant side effects including flushing and itching, while nicotinic riboside is safer and can readily penetrate the brain.
With this new grant, Dr. Shackelford’s lab will treat A-T cells in culture with nicotinic riboside to determine if NAD levels increase and survival improves. If this experiment works, the results will provide A-T researchers with a potential path toward a treatment for keeping brain cells alive in A-T patients.
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