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article imageTackling cocaine addiction with bacteria-protein cocktail

By Tim Sandle     Jan 26, 2015 in Science
In a new study, a modified bacterial protein is able to trigger a robust immune response against a cocaine-linked molecule in mice. The creators hope it will stop addicts from taking the drug.
Cocaine abuse is problematic, directly and indirectly impacting the lives of millions, and yet existing therapies are inadequate and usually ineffective. Cocaine is a powerfully addictive drug, produced from the leaves of the coca plant native to South America. Cocaine produces short-term euphoria, energy, and talkativeness in addition to potentially dangerous physical effects, including raising the heart rate and blood pressure.
The new drug is the outcome of decades of research and comes after many failed attempts to create a substance that will stop people from using cocaine. Now comes a new tract and the answer appears to be microbial.
It is hoped that a bacterial protein called flagellin and a cocaine hapten called GNE could be the key. A hapten is a small molecule that can elicit an immune response when attached to a large carrier such as a protein. In this case the protein is microbial: flagellin (a type of ‘globular protein.’)
Flagellin stimulates the innate immune response. This, in turn, leads to dose-dependent stimulation of anti-GNE antibody production. This means that the desire to take cocaine in an addict is much diminished. This works by the drug, on entering the blood stream through an intramuscular injection, triggering blood cells to produce antibodies to the cocaine molecule. This creates an army of antibodies that can latch onto free cocaine molecules in the bloodstream and, because they are too bulky to fit through tight junctions in blood vessels, prevent the drug from leaving the circulatory system and entering tissues and organs. This means the effect of the drug does not register with the brain of the user, neutralizing cocaine in effect.
The molecule was tried out in mice. Here noticeable animal behavioral effects, when challenged with a drug of abuse, were observed.
The development was undertaken by Kim Janda of Scripps Research Institute and his colleagues. The research group successfully developed a modified recombinant flagellin protein that displayed GNE. When injected into mice, the molecule elicited dose-dependent expression of anti-GNE antibodies.
The research findings have been published in the journal Molecular Pharmaceutics. The research is titled “Flagellin as Carrier and Adjuvant in Cocaine Vaccine Development.”
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