Drug duo is effective in urea cycle disorders
A 25-year study at 118 U.S. hospitals has demonstrated the effectiveness of a simple treatment for a mind-destroying, frequently lethal family of genetic diseases called urea cycle disorders.
The diseases are rare, affecting about one in every 8,200 people, but before the discovery of the drugs used in the study, there was little that could be done for sufferers. The drugs are frequently used to treat the condition in the United States but less commonly used in other parts of the world.
That is why the researchers chose to publish their data now, according to Dr. Ada Hamosh of the Johns Hopkins School of Medicine, the senior author of the paper published Thursday in the New England Journal of Medicine.
The urea cycle is made up of six enzymes that rid the body of nitrogen produced during the metabolism of amino acids in food. They convert it to urea, which is eliminated in urine.
If the cycle does not work, toxic ammonia builds up in the body -- a condition called hyperammonemia -- leading to brain damage, coma and death. If the first enzyme in the cycle is affected, the disorder manifests itself soon after birth. If the last enzyme is affected, the disorder typically does not appear until late adulthood.
Twenty-eight years ago, Dr. Saul W. Brusilow, a pediatrician now retired from Hopkins, tested two chemicals made by the body in small quantities, sodium phenylacetate and sodium benzoate. Both bind to ammonia and help remove it.
The drugs “just knocked my socks off from the moment we first tried them,” Brusilow recalled. “In all my years, I never came across another disease where patients came in near-comatose, and you stick a needle in them and, lo and behold, they wake up just like that.”
The federally funded study enrolled 299 patients who suffered 1,181 episodes of hyperammonemia between 1980 and 2005. Of those, 84% of infants and 96% of adults receiving the treatment survived. In contrast, the survival rate for untreated patients in Europe was 16% for newborns and 72% for adults, according to a recent paper.
The data were submitted to the Food and Drug Administration two years ago, leading to the approval of a combination drug called Ammonul, manufactured by Ucyclyd Pharma Inc. of Scottsdale, Ariz.
The main challenge now is recognizing the disorder, said Dr. Gregory Enns of the Stanford University School of Medicine, lead author of the paper. Lethargy, vomiting and rapid breathing in newborns are often misinterpreted as hospital-acquired infections, he said.
