The simple notion of copying the body’s own natural "waste disposal" chemistry to mop up potentially toxic nitrogen has saved an estimated 80 percent of patients with urea cycle disorders --- most of them children – according to a report in this week’s New England Journal of Medicine summarizing a quarter century of experience with the treatment.
The effectiveness of sodium phenylacetate and sodium benzoate, two chemicals the body already makes to carry nitrogen for disposal in urine "just knocked my socks off from the moment we first tried them," recalls Saul Brusilow, M.D., professor emeritus of pediatrics at Hopkins who first had the notion to use the drugs. "In all my years I never came across another disease where patients come in near-comatose and you stick a needle in them and lo and behold, they wake up—just like that. It was just astonishing," he says.
"His elegant idea was to give patients chemicals they already make in small amounts in large doses to make up for the missing urea cycle enzyme they inherited," says Ada Hamosh, M.D., M.P.H, clinical director of the McKusick-Nathans Institute of Genetic Medicine. "Sodium phenylacetate and sodium benzoate already know how to eliminate nitrogen in urine, so having more in the body carries more nitrogen out and reduces the toxic effects of excess nitrogen accumulation."
Excess nitrogen yields ammonia, which is poisonous and in the case of urea cycle disorders, causes brain damage, retardation, coma and even death.
Despite the immediate clinical success of the treatment, the drug combination was finally approved by the U.S. Food and Drug Administration only in 2005.
Brusilow, Hamosh, and colleagues at Stanford University, University of Minnesota, Thomas Jefferson University and the Medical College of Wisconsin looked back at 299 urea cycle disorder patients with a total of 1,181 hyperammonemia "episodes" from 118 hospitals around the United States from August 1
Source:Johns Hopkins Medical Institutions