Navigation Links
An 'elegant' idea proves its worth 25 years later

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 1 980 until March 2005.

The regimen consisted of high-dose intravenous sodium phenylacetate and sodium benzoate for two hours followed by "maintenance infusions" until blood ammonia levels were normal. The patients’ overall survival rate was 84 percent, and 96 percent survived episodes of severe ammonia poisoning.

An estimated one in 40,000 live births is a child with a urea cycle disorder, according to Hamosh, who says early and accurate detection can now assure prompt treatment.

"We’re teaching all medical students at Hopkins to consider hyperammonemia and immediately do blood tests when they see a combative, lethargic or comatose newborn or child," she says. "The longer the hyperammonemia lasts, the higher the risk for brain damage."

"This is a happy story," says Brusilow. "It isn’t too often in genetic medicine that we can intuitively develop a treatment with already available chemicals and save lives."

Source:Johns Hopkins Medical Institutions

Related biology news :

1. Nobel Laureate finds elegant explanation for DNA transcribing enzymes high fidelity
2. Adding Radiation Therapy To Chemotherapy Improves Survival In Patients With High-risk Breast Cancer
3. FDA Approves Human Hookworm Vaccine for Phase I Safety Trials
4. Purdue proves concept of using nano-materials for drug discovery
5. FDA Approves New Drug to Treat Type I and Type II Diabetes
6. Canada approves marijuana-based pain spray
7. Bevacizumab Combined With Chemotherapy Improves Progression-Free Survival for Patients With Advanced Breast Cancer
8. Product improves peptide identification for proteomics research
9. FDA Approves New Treatment for Chronic Hepatitis B
10. Stem cell treatment improves mobility after spinal cord injury
11. FDA approves more generic AIDS drugs

Post Your Comments:

(Date:11/12/2015)... 12, 2015  A golden retriever that stayed healthy ... (DMD) has provided a new lead for treating this ... Broad Institute of MIT and Harvard and the University ... Cell, pinpoints a protective gene ... disease,s effects. The Boston Children,s lab of Lou ...
(Date:11/11/2015)... MedNet Solutions , an innovative SaaS-based eClinical technology company that ... announce that it will be a Sponsor of the ... held November 17-19 in Hamburg , Germany.  ... iMedNet , MedNet,s easy-to-use, proven and affordable eClinical ... able to deliver time and cost savings of up to ...
(Date:11/9/2015)... DUBLIN , Nov. 09, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) ...
Breaking Biology News(10 mins):
(Date:11/26/2015)... CHESHAM , England , November 26, ... Lightpoint Medical, an innovative medical device company specializing in ... Euro grant from the European Commission as part of the ... enabling the company to carry out a large-scale clinical trial ... -->      (Logo: , ...
(Date:11/25/2015)... -- PharmAthene, Inc. (NYSE MKT: PIP) announced  today that its ... (Rights Plan) in an effort to preserve the value ... 382 of the Internal Revenue Code (Code). ... its NOLs could be substantially limited if the Company ... of the Code. In general, an ownership change occurs ...
(Date:11/25/2015)... Studies reveal the differences in species of ... way for more effective treatment for one of the most ... --> --> Gum disease is ... yet relatively little was understood about the bacteria associated with ... by researchers from the WALTHAM Centre for Pet Nutrition together ...
(Date:11/25/2015)... 2015  Neurocrine Biosciences, Inc. (Nasdaq: NBIX ) ... CEO of Neurocrine Biosciences, will be presenting at the ... New York . .   ... 5 minutes prior to the presentation to download or ... will be available on the website approximately one hour ...
Breaking Biology Technology: