Cocaine vaccine passes key testing hurdle

Research shows vaccine prevents cocaine reaching the brain

Researchers at Weill Cornell Medical College in the US have successfully tested their novel anti-cocaine vaccine in primates, bringing them closer to launching human clinical trials.

Their study, published online by the journal Neuropsychopharmacology, 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,’ says the study’s lead investigator, Dr Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College.

‘We believe this strategy is a win-win for those individuals among the estimated 1.4 million cocaine users in the US who are committed to breaking their addiction to the drug,’ he says.

‘Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect.’

Dr Crystal says he expects to begin human testing of the anti-cocaine vaccine within a year.

Once immune cells are educated to regard cocaine as the enemy, it produces antibodies against cocaine the moment the drug enters the body

The novel vaccine developed by Dr Crystal and his colleagues 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 mounts an immune response against both the virus and the cocaine impersonator that is hooked to it. ‘The immune system learns to see cocaine as an intruder,’ says Dr Crystal. ‘Once immune cells are educated to regard cocaine as the enemy, it produces antibodies against cocaine the moment the drug enters the body.’

In their first study in animals, the researchers found a strong immune response was generated against the vaccine in laboratory mice. Also, when the scientists extracted the antibodies produced by the mice and put them in test tubes, they gobbled up cocaine. Furthermore, mice that received both the vaccine and cocaine were much less hyperactive than untreated mice given cocaine.

Cocaine blocks the recycling of dopamine in two areas of the brain: the putamen in the forebrain and the caudate nucleus in the brain's centre. When dopamine accumulates at the nerve endings, it causes the ‘feel good’ part of the cocaine high.

In this study, the researchers sought to define precisely 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.

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.

I believe that for those people who desperately want to break their addiction, a series of vaccinations will help

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% of the dopamine transporter had to be occupied by cocaine to produce a drug high. The researchers found that in vaccinated primates cocaine occupancy of the dopamine receptor was reduced to levels of less than 20%.

‘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,’ says 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 adds.

The researchers do not know how often the vaccine needs to be administered in humans to maintain its anti-cocaine effect. One vaccine lasted 13 weeks in mice and seven weeks in non-human primates.

‘An anti-cocaine vaccination will require booster shots in humans, but we don't know yet how often these booster shots will be needed,’ says Dr Crystal. ‘I believe that for those people who desperately want to break their addiction, a series of vaccinations will help.’

Co-authors of the study include Dr Anat Maoz, Dr Martin J. Hicks, Dr Shankar Vallabhajosula, Michael Synan, Dr Paresh J. Kothari, Dr Jonathan P. Dyke, Dr Douglas J. Ballon, Dr Stephen M. Kaminsky, Dr Bishnu P. De and Dr Jonathan B. Rosenberg from Weill Cornell Medical College; Dr Diana Martinez from Columbia University; and Dr George F. Koob and Dr Kim D. Janda from The Scripps Research Institute. The study was funded by grants from the National Institute on Drug Abuse (NIDA).

The Cornell Center for Technology Enterprise and Commercialization, on behalf of Cornell University, has filed a patent application based on the research. Dr Crystal is named as a co-inventor on the patent application.