Treatment News

Dangerous Urea Cycle Disorder Successfully Treated with Nitric Oxide Product

1.0 from 3 votes
Wednesday, June 06, 2012

Learn more about:

Access Programs

Austin, TX - In the spring of 2010, Baylor College of Medicine's (BCM) Dr. Brendan Lee received a desperate email from the mother of one of his patients.

The teen – who had been Lee's patient for most of his life – was in hypertensive crisis and none of the usual treatments could bring his blood pressure down to normal. His heart was enlarged and not pumping well – a problem called cardiomyopathy that was the result of more than a decade of difficult-to-control high blood pressure. All of the standard blood pressure treatments were ineffective even when combined.

The problem was the patient’s genetic disorder – argininosuccinic aciduria – which meant that he lacked a functional gene to make an enzyme called argininosuccinate lyase. Without that enzyme, he could not make arginine, a critical amino acid. Arginine plays an important role in the urea cycle, which enables the body to avoid toxic buildup of the materials that can make ammonia. A buildup of ammonia in the body damages the body's organs and brain. Arginine is also necessary for producing nitric oxide (NO) within the body. NO is one of the most important signaling molecules and is responsible for maintaining normal blood pressure.

Giving the patient arginine prevented the damaging buildup of ammonia, but by age 3, he was experiencing two other symptoms – high blood pressure and neurodevelopmental delay. Lee and collaborators, including Nathan S. Bryan, Ph.D. at the Brown Foundation Institute of Molecular Medicine at The University of Texas Health Science Center at Houston (UTHealth), had previously discovered that this particular condition led to insufficient NO production. In November 2011, they published their results in the journal Nature Medicine.

Long quest

Finding the solution to the disorder plaguing the now 17-year-old patient was a long quest that Lee, a professor of molecular and human genetics at BCM, undertook when he first saw him as a young child in the metabolic clinic at Texas Children’s Hospital.

“Understanding that NO deficiency is a result of this disorder was groundbreaking, but somewhat frustrating because up until now, there haven’t been any safe and effective therapeutics or strategies for chronic treatment of low NO,” said Bryan, also Chief Science Officer for Neogenis Labs, Inc. Fortunately, Bryan had discovered and developed a novel nitric oxide technology that uses natural product chemistry to produce a supplement which helps the body to generate NO. This patent pending technology is licensed by Neogenis® Labs, Inc from the University of Texas System.

When all standard available treatments had failed this patient, Dr. Lee asked Neogenis Labs to formulate a specific dietary supplement for this patient that would help his body’s own physiology to restore nitric oxide levels. The results were astounding. With the addition of the supplement to his diet and existing regimen, the patient’s blood pressure dropped to normalized levels, his cardiomyopathy has corrected and his cognition improved. "Over a period of four days, his blood pressure and pulse became normal," said Lee. "In the two years since, his heart has become stable." Today the patient is off all blood pressure treatments, takes the Neogenis supplement daily and is doing very well. This team of scientists and physicians provided the case description with associated research in the animal model online in the American Journal of Human Genetics. The study was published in the May 4th print issue of the journal.

Rather than trying to directly make up for the enzyme deficiency that left the teen unable to make nitric oxide, the supplement assisted the patient’s body in making the nitric oxide necessary to maintain stable blood pressure.

The patient’s mother also said that after the treatment, her son showed some improvement in cognitive testing and he seemed more aware of the world around him. "Last year, when he was still in middle school, he passed the regular reading TAKS test," she said. “He also seems more aware of the attitudes of his fellow students.”

Platform technology

“The strategy of developing natural product chemistry to safely and effectively help the body produce nitric oxide is innovative, and we believe is a platform technology that may be used in a number of conditions associated with NO insufficiency,” said Joel Kocher, CEO of Neogenis Labs, Inc. “We have commercialized this technology as a dietary supplement called Neo40®,” said Kocher.

Others who took part in the research include Drs. Philippe M Campeau, Oleg Shchelochkov, both of BCM, along with Nagamani are joint first authors of the study. Lee and Dr. Ayelet Erez are joint senior authors. Others taking part include Muralidhar H. Premkumar, Nicola Brunetti-Pierri, Yuqing Chen, Qin Sun, Donna Palmer, Slesnick C Timothy, Daniel I Feig, Susan Caudle, Anilkumar K Reddy and Juan Marini of BCM, Yaoping Tang and Nathan S Bryan of UTHealth, Li Li and David Harrison of Emory University School of Medicine in Atlanta and Leonardo Salviati of the University of Padova in Italy.

Funding for this study came from the National Institutes of Health; the Baylor College of Medicine Intellectual and Developmental Disabilities Research Center; the National Urea Cycle Disorders Foundation; the Canadian Institute of Health Research; the Urea Cycles Disorder Consortium of the Rare Diseases Clinical Research Network O’Malley Fellowship; the German Research Foundation; the Telethon Italy and the Fondazione CARIPARO and the Howard Hughes Medical Institute. Neogenis Labs formulated and donated the nitric oxide supplement used in the study.

Source: American Journal of Human Genetics.
1.0 from 3 votes
Free Newsletter
Trending News