New Monoclonal Antibody Destroys Methamphetamine In Vitro

By Eric Sauter

Scientists at The Scripps Research Institute have developed a new monoclonal antibody that destroys the highly addictive drug methamphetamine. These new findings suggest an entirely new way to treat the global epidemic of methamphetamine abuse. 

The study is being published the week of February 26, 2007 in an advanced online edition of the Proceedings of the National Academy of Sciences.

The new antibody, called YX1-40H10 and tested in vitro, converts the drug methamphetamine into a benign substance called benzaldehyde. Benzaldehyde, which has a characteristic almond scent, is a simple compound often used in food flavoring.

"While animal studies have not yet been done, our results so far are significant and encouraging," said Scripps Research scientist Kim Janda, who led the study. "The difference between the final non-psychoactive compound benzaldehyde and methamphetamine couldn't be more striking."

In this country, methamphetamine abuse has become a fast rising and devastating epidemic. According to a 2005 National Survey on Drug Use and Health, an estimated 10.4 million Americans aged 12 or older (4.3 percent of the population) have tried the drug. More ominous, perhaps, was a 2005 Monitoring the Future survey of student drug use that reported that 4.5 percent of all high school seniors had used the drug in their lifetimes. Methamphetamine, which is chemically similar to amphetamine and the neurotransmitter dopamine, stimulates the central nervous system, increasing blood pressure and heart rate, and raising blood sugar levels.

"While our laboratory has developed an antibody approach to cocaine addiction, this new antibody is something of a milestone," said Janda. "Because methamphetamine has a much longer half-life in the body than cocaine—approximately 12 hours versus half an hour—finding a way to remove such a neurotoxically potent drug is critical to any potential therapeutic effort."

Janda's laboratory is one of the pioneers in the study of immunopharmacotherapy, which uses antibody-based therapeutics as an innovative approach to control drug abuse. The immunopharmacotherapy approach is based on the idea that the body can be taught to produce antibodies that bind to a target before it can reach the brain. Recognizing a molecule that it ordinarily couldn't, the immune system can short circuit feedback from drugs of abuse—if there's no drug in the brain, there are no physiological rewards from drug intake. Antibody catalysts that convert drugs of abuse into inactive forms are potentially even more efficient agents than those that simply bind and sequester or eliminate the drug.

The new study shows that the YX1-40H10 antibody facilitates the conversion of methamphetamine to benzaldehyde through a process of photooxidation by binding riboflavin (vitamin B2) and visible light.

"What our findings suggest is that under appropriate conditions of riboflavin, light, and the right antibody, we can destroy a number of different antigens through photooxidation, and destroy them completely," Janda said.

Interestingly, the photooxidation reaction described in the new study can be inhibited by molecular oxygen. This could have future significance in developing methods to destroy selected molecular targets at oxygen-deficient sites. The photooxidation process described may also have additional implications for immune defense, autoimmune disease, and the treatment of cancer.

In addition to Janda, authors of the study, Antibody-catalyzed anaerobic destruction of methamphetamine, include Yang Xu, Mark S. Hixon, Noboru Yamamoto, Laura McAllister, Anita D. Wentworth, and Paul Wentworth, Jr. See the Proceedings of the National Academy of Sciences at http://www.pnas.org/cgi/content/abstract/0611094104v1.

The study was supported by The Skaggs Institute for Chemical Biology at Scripps Research and the National Institutes of Health.

Send comments to: mikaono[at]scripps.edu

"The difference between the final non-psychoactive compound benzaldehyde and methamphetamine couldn't be more striking."

—Kim Janda