New 'wrinkle' in Botox treatment could lead to lower doses, better safety

There may soon be a better way to fight unsightly wrinkles. Researchers have discovered a novel way to increase the potency of botulinum neurotoxin treatments — commonly known as Botox — that they say could one day allow patients to receive the injections less frequently while maintaining or even enhancing its cosmetic benefits.

By allowing lower doses, the new approach could also make the treatment safer by reducing the risk of complications associated with immune system recognition that can sometimes occur with frequent injections, according to scientists at the Scripps Research Institute in La Jolla, Calif. Smaller, more potent doses may even lead to lower prices for the popular wrinkle-remover, the researchers say. Their study is published in the March 29 issue of the weekly Journal of the American Chemical Society.

Although popular for removing wrinkles, Botox is also used to treat a growing number of other conditions, including migraine headaches, lazy eyes and excessive sweating. It is developed from the botulinum neurotoxin, the most lethal poison known and a potential bioterrorist weapon. In a medical setting, small doses of a purified version of the toxin block the release of a chemical (acetylcholine) that signals muscle contraction, resulting in a localized, temporary paralysis that erases wrinkles and unwanted muscle spasms.

Kim Janda, Ph.D., a chemistry professor at Scripps and head of the research study, and his associates developed a synthetic molecule that can ‘superactivate’ the neurotoxin used in Botox by binding to specific sites on the neurotoxin protein. The synthetic molecule works by increasing the activity of an enzyme that cleaves proteins that are critical for neurotransmitter release, thereby increasing the blockage of acetylcholine and enhancing the toxin’s paralyzing effect. In laboratory studies, the researchers found that this ‘superactivator’ could boost the activity of the toxin by as much as 14 times that of the untreated toxin.

The new treatment has not yet been tested in humans or animals, the researchers say. If further studies prove successful, the technique could be available to consumers in four to six years, the researchers estimate.

"We have developed a synthetic molecule that binds to the toxin and increases its normal function," Janda says. "The discovery of small molecule activators may ultimately provide a valuable method for minimizing dosage, reducing resistance, and increasing its clinical efficacy."

One possible complication of Botox injections is that their repeated use can lead to recognition by the immune system, especially when patients are given frequent, high doses of the toxin. Higher doses can also increase the risk of adverse complications, which can include pain in the face, redness at the injection site and muscle weakness. The new ‘superactivator’ formula could allow lower doses to be administered — roughly one-tenth the normal dose — while reducing the possibility of unwanted immune complications, Janda and his associates say. Botox injections should always be performed by a qualified doctor, according to the U.S. Food and Drug Administration.

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Funding for this study was provided by the National Institutes of Health and The Skaggs Institute for Chemical Biology. Study co-authors include: Laura A. McAllister, Mark S. Hixon, Jack P. Kennedy and Tobin J. Dickerson.

The American Chemical Society — the world’s largest scientific society — is a nonprofit organization chartered by the U.S. Congress and a global leader in providing access to chemistry-related research through its multiple databases, peer-reviewed journals and scientific conferences. Its main offices are in Washington, D.C., and Columbus, Ohio.

The online version of the research paper cited above was initially published March 9 on the journal’s Web site. Journalists can arrange access to this site by sending an e-mail to newsroom@acs.org or calling the contact person for this release.

Kim D. Janda, Ph.D., is a professor in the Department of Chemistry at The Scripps Research Institute in La Jolla, Calif. He is also director of the Worm Institute of Research and Medicine.


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