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OHSU Investigates Similarities Between Rare Genetic Disorder and Rave Party Drug

   Portland, Ore.

Researchers at Oregon Health & Science University are hoping to gain new insight into the abuse of the popular rave party drug GHB (gamma hydroxybutyrate) through research into a rare genetic disorder. Using the disorder called succinate semialdehyde dehydrogenase (SSADH) deficiency as a model, scientists have found an amino acid that counteracts the effects of high GHB levels. Through this discovery, researchers hope to further understand the effects of GHB on the human body and develop treatments for patients with SSADH deficiency as well as those who abuse the drug. K. Michael Gibson, Ph.D., a professor of molecular and medical genetics in OHSU's School of Medicine, conducted the research along with collaborators at the Baylor University Medical Center, Dallas, Texas. Their conclusions will appear in the October edition of the journal Nature Genetics. An advanced copy of the article was posted online on September 2.

SSADH deficiency is a rare genetic defect that causes an accumulation of GHB in body fluids and tissues. While all healthy humans generate small amounts of GHB naturally, patients with this disorder produce the chemical at much higher levels. Mental and motor retardation, delayed or absent language development, and weak muscles characterize the disease. Some patients also suffer from seizures. To date, approximately 350 cases have been identified worldwide.

"In the course of our investigations into the human genetic disease, we noted many similarities between the symptoms of SSADH deficiency and GHB drug abuse," said Gibson. "As GHB's popularity skyrocketed over the last decade, we recognized the value of using the disorder as a model for those abusing the drug, and vice versa. The knowledge we gain from study of the human disease should be applicable to illicit GHB usage."

Researchers developed a mouse model for SSADH deficiency. Using this model, scientists discovered that an amino acid called taurine, commonly found in milk, was able to partially counteract the effects of GHB buildup in the diseased mice, saving them from early death. Taurine is also a common ingredient in popular high-energy drinks sold at supermarkets across the country.

"We're hopeful that taurine or related compounds might provide future treatments for those who suffer from SSADH deficiency. We also suggest that taurine and related compounds may have the ability to counteract the effects of illicitly consumed GHB," said Gibson.

While continued study of this proposed therapy is necessary, OHSU is considering further development that will assist in moving this discovery from the lab bench to the patient's bedside.

"When Dr. Gibson's ongoing studies indicate the most effective way of using taurine or related compounds to counter the effects of GHB toxication, our office will work with pharmaceutical companies by licensing new medications or formulations that can gain FDA approval, thus ensuring their availability to the public for treating the victims of GHB overdose in the emergency room," said William Thompson, Ph.D., Senior Licensing Associate, OHSU's Office of Technology & Research Collaborations.

A synthetic form of GHB was first developed in the 1960s and is used clinically in the treatment of narcolepsy, alcohol and opiate withdrawl, and for anesthesia in certain surgical situations. GHB also has been sold in health food stores to aid in weight loss and muscle building. In the 1990s it resurfaced as a popular rave party drug. Due to adverse effects associated with abuse, the Justice Department made GHB a Class I controlled substance in 1999 making it illegal to manufacture, sell or posses the drug for use not approved by the FDA.

GHB is often referred to as a "date rape" drug, in relation to its amnesia-like effects. GHB is abused predominantly by teen-agers and young adults, and often at nightclubs and at rave parties. The drug is a nervous system depressant that can relax or sedate the body. When used in higher doses, it can slow breathing and heart rate to dangerously low levels sometimes resulting in death. The depressant actions of GHB are compounded by co-consumption of other adulterants, especially ethanol.

The research was funded by the National Institute of Neurological Disorders and Stroke, a component of the National Institutes of Health; and the March of Dimes National Birth Defects Foundation.

Other collaborators for this research included Vrije Universiteit Medical Center and Erasmus University, The Netherlands; Novartis Pharma Inc., Switzerland; the Hospital for Sick Children, Ontario, Canada; and the University of Texas Southwestern Medical Center, Dallas, Texas.

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