Infecting the brain to stop addiction?

D rug abuse is a major public health problem, and, although there are many treatments of proven efficacy, the majority of patients are not permanently cured, with relapse rates on the order of 70% or more in the first years for the treatment of almost all drugs of addiction. Therefore, there is a great need for new and improved therapies. Carrera et al. (1) have pioneered the use of one of the oldest proven medical interventions, immunization, in the treatment of cocaine dependence. Their initial studies revealed that it is possible to vaccinate animals against cocaine by using either a blocking antibody (1) or catalytic antibody (2) approach. The blocking antibody binds cocaine and therefore extracts it from the blood; this seems to be the more promising method, because the current catalytic antibodies only minimally accelerate the clearance of cocaine. However, the blocking antibody technique provides only a peripheral blockade, and so any cocaine that is not ‘‘mopped up’’ by antibodies in plasma can enter the brain and give the reinforcing actions that perpetuate the cycle of addiction and dependence. The work by Carrera et al. (3) in a recent issue of PNAS moves the field by utilizing a concept originated for the treatment of Alzheimer’s disease in which an antibody to -amyloid was delivered to the brain in a (bacterio)phage vector (4). Here, the animal is infected with a phage that targets the brain and that has been engineered to express thousands of copies of the cocaine-binding antibody. It reproduces in the brain, thereby generating large amounts of blocking antibody. When cocaine enters the brain, some of it binds to the antibody and, therefore, is not available to perform its usual action: to increase dopamine, the neurotransmitter that is thought to mediate its actions. To maximize access of phage to the brain and minimize peripheral infection, the phage vaccine was administered intranasally, where it is presumed to enter the olfactory nerve endings and move down the axons into the brain.