New anti-cocaine vaccine passes key test in primates
Washington: A novel anti-cocaine vaccine developed by researchers at Weill Cornell Medical College has been successfully tested in primates, bringing them closer to launching human clinical trials.
Their study used a radiological technique to demonstrate that the anti-cocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high.
"The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain," said the study`s lead investigator, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College.
Dr. Crystal asserted that he expects to begin human testing of the anti-cocaine vaccine within a year.
The novel vaccine Dr. Crystal and his colleagues developed combines bits of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into an animal, its body "sees" the cold virus and mounts an immune response against both the virus and the cocaine impersonator that is hooked to it.
In their first study in animals, the researchers injected billions of their viral concoction into laboratory mice, and found a strong immune response was generated against the vaccine. Also, when the scientists extracted the antibodies produced by the mice and put them in test tubes, it gobbled up cocaine. They also saw that mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.
In this study, the researchers sought to precisely define how effective the anti-cocaine vaccine is in non-human primates, who are closer in biology to humans than mice.
They developed a tool to measure how much cocaine attached to the dopamine transporter, which picks up dopamine in the synapse between neurons and brings it out to be recycled. If cocaine is in the brain, it binds on to the transporter, effectively blocking the transporter from ferrying dopamine out of the synapse, keeping the neurotransmitter active to produce a drug high.
In the study, the researchers attached a short-lived isotope tracer to the dopamine transporter. The activity of the tracer could be seen using positron emission tomography (PET). The tool measured how much of the tracer attached to the dopamine receptor in the presence or absence of cocaine.
The PET studies showed no difference in the binding of the tracer to the dopamine transporter in vaccinated compared to unvaccinated animals if these two groups were not given cocaine. But when cocaine was given to the primates, there was a significant drop in activity of the tracer in non-vaccinated animals. That meant that without the vaccine, cocaine displaced the tracer in binding to the dopamine receptor.
Previous research had shown in humans that at least 47 percent of the dopamine transporter had to be occupied by cocaine in order to produce a drug high. The researchers found, in vaccinated primates, that cocaine occupancy of the dopamine receptor was reduced to levels of less than 20 percent.
"This is a direct demonstration in a large animal, using nuclear medicine technology, that we can reduce the amount of cocaine that reaches the brain sufficiently so that it is below the threshold by which you get the high," said Dr. Crystal.
When the vaccine is studied in humans, the non-toxic dopamine transporter tracer can be used to help study its effectiveness as well, he added.
But the researchers do not know how often the vaccine needs to be administered in humans to maintain its anti-cocaine effect.
Their study was published online by the journal Neuropsychopharmacology.
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