R&D News: Scripps Research and Cornell scientists create novel vaccine
The researchers said that this novel strategy might be the first to offer cocaine addicts a fairly simple way to break and reverse their habit. The approach could also be useful in treating other addictions, such as to nicotine, heroin, and methamphetamine.
â€œOur very dramatic data shows that we can protect mice against the effects of cocaine, and we think this approach could be very promising in fighting addiction in humans,â€ says the studyâ€™s lead investigator, Ronald Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College.
â€œThe vaccine suppresses the stimulant effects of the drug,â€ said Scripps Research professor Kim Janda, a co-author of the paper and a pioneer in the field of developing vaccines against addictive drugs such as cocaine. â€œUnlike other types of treatment, a vaccine such as this one does not interfere with the neurological targets of the drug, but instead blocks cocaine from ever reaching the brain in the first place.â€
In the new study, the vaccine effect lasted for at least 13 weeks, the longest time point evaluated in such an approach. Since the vaccine likely will not require multiple expensive infusions, the researchers hope that it can move quickly into human trials.
Clinically, this sort of therapy could be given to people in treatment programs to aid in their recovery. And, like most other types of treatment, it will only be useful for those who want the help.
â€œThis vaccine would be most applicable for addicts who are who are interested in getting off the drug,â€ said Janda, the Eli R. Callaway Jr. Chair in Chemistry and a member of the Skaggs Institute for Chemical Biology at Scripps Research. â€œIn essence we view such vaccines as â€˜immuno-helpersâ€™ for treating substance abuse, and, in the case at hand, it might prove to be extremely useful for crack addicts whose relapse rate is exceedingly high.â€
Cocaine, derived from the leaf of the Erythroxylaceae coca plant, is a highly potent drug that, as a salt, is either snorted or dissolved in water and injected directly into the bloodstream. The salt is also often neutralized to make an insoluble 'free-base' form that is smoked.
Once ingested in the bloodstream, the drug crosses the bloodâ€“brain barrier and accumulates rapidly in the brain. â€œThe brain levels rise very rapidly once cocaine is taken into the system,â€ said Mr Janda.
Moreover, the cocaine builds up in parts of the brain reward systems such as the nucleus accumbens. There, the cocaine molecules interfere with the normal regulation of dopamine by binding to dopamine transporters and blocking them from recycling the neurotransmitter.
This leads to the build-up of dopamine in the nucleus accumbens, which produces a euphoric feeling in the user-a quick rush that hits seconds after taking the drug and lasts several minutes. The psychological effect of this immediate reward is the basis for drug seeking in users. Compulsive users-addicts-will keep a perceived desire for the effect that will many times confound a recovering addictâ€™s best efforts to stay clean.
There is a common report among intravenous drug addicts that their first injection-that first snort of coke, shot of heroin, or puff of crack-produced the greatest feeling they had ever experienced. Many will also tell you that they too often spent their money, health, family, friends, and lives to try to get that feeling back.
â€œUnfortunately, there is no methadone for cocaine,â€ said Mr Janda. â€œImmunotherapy, however, might provide the added boost to keep a person from a major relapse, as after immunization a slip will not produce a drug effect.â€
In previous work, Mr Janda and his synthetic team had developed several alternative formulations of anti-cocaine vaccines, which also acted by stimulating an active immune response against the drug in the bloodstream. However, a drawback of these prior vaccines as a lack of ready transferability to clinical trials.
In the new study, the team took advantage of a cocaine-hapten-scaffold (a cocaine-antigen that would elicit cocaine-producing antibodies) that Janda developed in the early 90s, this time chemically modifying it so that it could be attached to components of the adenovirus, a common cold virus. In this way, the human immune system was alerted to an infectious agent (the virus), but also learned to â€œseeâ€ the cocaine as an intruder.
In this approach, the researchers used only the parts of the adenovirus that elicited an immune response, discarding those that produce sickness.
To test the effect of the vaccine, the researchers then injected billions of these viral concoctions into laboratory mice and found a strong immune response was generated against the vaccine. When put in test tubes, these antibodies gobbled up cocaine.
The scientists then tested the vaccineâ€™s effect on behavior and found mice that received the vaccine before cocaine were much less hyperactive while on the drug than unvaccinated mice. The effect was even seen in mice that received large, repetitive doses of cocaine. The cocaine doses reflected amounts humans might use.
While the path to a commercially available drug is a long one and the vaccine still needs to be tested extensively in humans, the researchers are hopeful their work will one day lead to a new way to battle cocaine addiction.
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