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Cocaine-vaccine technology is one stepcloser to the clinic with the announce-ment last month of phase II trial resultsin abstinent and active cocaine users. Aweek later, another research teamreported a vaccine concept that aims toimprove previous results by using avirus to express cocaine-bindingantibodies in the brain.

The vaccine concept used in theclinical trials involves cocaine bound toa large protein—this stimulatesantibodies that mop up cocaine in thebloodstream and reduce the “high”.Thomas Kosten (Yale University Schoolof Medicine, New Haven, CT, USA)and his team gave TA-CD vaccinecourses (Xenova, UK) to nine ex-usersfor relapse prevention and 13 currentusers for abstinence initiation. Six ofeight ex-users and seven of 12 currentusers who completed the study wereabstinent at 12 weeks. Although mostusers had relapsed by 6–12 months, asubstantial proportion reportedreduced stimulant effects of cocaine(College on Problems of Drug

Dependence 66th Annual ScientificMeeting, Puerto Rico; June 12–17).

Previously, Kim Janda (The ScrippsResearch Institute, La Jolla, CA, USA)and colleagues used a similar strategybut found that antibodies in blood didnot always prevent cocaine fromcrossing the blood–brain barrier; thus,large drug doses could be used tocircumvent such peripheral approaches.On June 21, the group reportedsuccessful delivery to the CNS of rats ofa bacterial phage engineered to expressa cocaine-binding antibody. Sixinjections of an engineered filamentousphage were delivered into nasal passagesover 3 days; on the fourth day, the ratsreceived a cocaine injection. The virus-infected rats showed reduced signs of cocaine effects—locomotion andstereotyped behaviours—comparedwith controls (Proc Natl Acad Sci USA2004; published online June 28; DOI:10.1073/pnas.0403795101).

Janda points out that although theeffect is short-lived, the phage can bedelivered repeatedly without apparent

ill-effects or any binding to CNScomponents. “This is the first reportcombining advances in nasal drugdelivery, phage display, and animalbehavioural studies to show proof ofconcept”, says John Cashman (HumanBiomolecular Research Institute, SanDiego, CA). “Phages have provenremarkably safe to administer toanimals thus far. Although thetechnology has been around for aconsiderable amount of time,applications for CNS delivery are intheir infancy and prudence suggestscaution.” Janda speculates that clinicaltrials are at least a year or two away.

In the report Pharmacotherapy andthe Drug War published last month, theCenter for Cognitive Liberty and Ethics(www.cognitiveliberty.org) commentedthat “the tremendously politicisednature of the ‘drug war’ raisessubstantial concerns that, in addition tothose who choose to use suchmedications, some people will becompelled to use them”.Kelly Morris

Hope and caution over cocaine vaccine has never been higher

People with Alzheimer’s disease retaintheir implicit memory, according to anfMRI study done by Cindy Lustig andRandy Buckner of WashingtonUniversity. “Our results raise theinteresting possibility that althoughhigh-level cognition may initially bemore difficult for older adults andAlzheimer’s patients, they can stillmaintain some kinds of learning andbenefit from practice”, says Lustig.

Lustig and Buckner compared theimplicit memory capabilities of 34young adults, 33 healthy old adults,and 24 old adults in early stages ofAlzheimer’s disease. They measuredthe participants’ implicit memory byasking them to decide as quickly aspossible whether a single word,presented visually, referred to a livingor non-living thing. People makedecisions quicker when classifyingitems that they have seen before(figure).

The researchers found that withpractice all three groups showed a

significant reduction in the timerequired to decide how to classify aword. Although the young people were

quickest at the task, the older adultswith Alzheimer’s disease performed aswell as healthy adults of the same age(Neuron 2004; 42: 865–75).

The experiment was done in anMRI machine, allowing the researchersto examine brain activity while theparticpants classified the words.Changes in activation along theinferior frontal gyrus, which is knownto be involved in implicit memory,were similar in patients with AD and

in younger people. “What wassurprising and novel in this study isthat the brain region with the greatestactivity during the task was the high-level region of the frontal cortex”, saysBuckner. “We didn’t expect thisbecause high-level cognition is affectedin AD.”

Jason Warren (Institute ofNeurology, London, UK) agrees withthe authors that it might be possible toexploit these findings to developcognitive rehabilitation programmesthat minimise demands on executivecontrol systems in favour of structuredtasks designed to exploit implicitmemory. “More speculatively”,Warren adds, “the observation thatparticular memory subsystems arerelatively more or less vulnerable todiffuse cortical pathologies such as ADraises the intriguing possibility offuture drug therapies targeted atspecific cognitive modules, as well asspecific diseases.”James Butcher

Implicit memory is retained by people with Alzheimer’s disease

Neurology Vol 3 August 2004 http://neurology.thelancet.com

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“Does the word represent aliving or non-living thing?”