Breaking the bonds of cocaine addiction may be easier with a vaccine that's currently being developed by researchers at Weill Cornell Medical College. This week, scientists took an important step on the way to the vaccine's first clinical trials in humans: a test that shows if and how the vaccine is working.
At the Society of Nuclear Medicine's annual meeting in Miami Beach, Fla., Weill Cornell researcher Shankar Vallabhajosula and his team showed how their molecular imaging technique tracks the anti-cocaine vaccine's ability to steer the drug away from the brains of rhesus monkeys. By enabling researchers to use objective measures to ascertain the vaccine's effectiveness, rather than behavioral observations that have been used in previous animal studies, the team hopes to build a much more conclusive foundation for human tests. The study hasn't been published yet in a peer-reviewed journal.
The vaccine, originally developed by Weill Cornell genetic medicine researcher Ron Crystal and described in the journal Molecular Therapy in January 2011, works by teaching the immune system to recognize cocaine as a threat. Inside the vaccine is a cocaine-like molecule linked to a piece of the virus that causes the common cold.
Once in the patient's system, the cold virus provokes the immune system to produce antibodies against it. Thus alerted to cocaine, the immune system prevents the drug from crossing the blood-brain barrier, eliminating the high that comes when cocaine binds to parts of neurons involved in transporting dopamine.
In mouse studies, Crystal and his team had measured the outcome of the vaccine by observing the animals' behavior; when given cocaine, vaccinated mice were not jumping around as much as they did before they received the prophylactic, Vallabhajosula said in a telephone interview.
But in order to make the leap to human subjects, researchers need a more concrete way of measuring the vaccine's efficacy. Crystal asked Vallabhajosula to try his hand at the problem.
We thought it would be nice to demonstrate objective evidence that the vaccine is actually working, Vallabhajosula said.
So Vallabhajosula used a technique called positron emission tomography, or PET, which tracked the spread of a molecular probe that resembles cocaine and also binds to dopamine transporters, as the drug does. They examined both vaccinated and unvaccinated monkeys that had been dosed with cocaine.
The researchers could see the probe accumulating in the brains of vaccinated rhesus monkeys. But in the unvaccinated monkeys, the signal was weaker -- the probe couldn't bind to neurons where cocaine had already bound.
This study reaffirms the beauty of the vaccine, Vallabhajosula said in a statement Monday.
Now Crystal's group is trying to figure out what the optimal dose of the vaccine is and how long the anti-cocaine antibodies remain circulating in a patient's bloodstream. The PET imaging technique can help fine-tune their search, according to Vallabhajosula.
If an anti-cocaine vaccine is approved in humans, it isn't a cure-all. Though it gets rid of cocaine's high, the vaccine doesn't protect against many of cocaine's side effects on the heart, lungs and circulatory system. Vallabhajosula says researchers haven't seen any major side effects thus far. Because the vaccine only contains part of the cold virus, not the whole thing, it's likely patients won't even get the sniffles while they're kicking the habit.
SOURCE: Vallabhajosula et al. Disrupted adenovirus-based anti-cocaine vaccine: Assessment of efficacy based on PET dopamine transporter (DAT) imaging and cocaine challenge, SNM's 59th Annual Meeting, June 9, 2012, Miami Beach, Fla.
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