Sunday, June 17, 2012

NIDA’s Volkow Defends New Medications for Addiction

On Big Data, Big Vaccines, and a Big New Agency.

In her Director’s Report to the 2011 meeting of the College on Problems of Drug Dependence in San Diego last week, Dr. Nora Volkow, director of the National Institute on Drug Abuse, sought to refute allegations that NIDA lately has been too focused on pharmacological approaches to treating addiction—“magic bullets” in the form of pills or vaccines. Dr. Volkow presented figures showing, as the CPDD Community Website reported, that “NIDA funding allocation for new medication development has remained stable at about 12% for some time, despite concerns expressed by some researchers that funding in other areas is being sacrificed to support the medication development portfolio.” Basic and clinical neuroscience research accounts for 45% of expenditures, she said.

In other news, Volkow expressed her avid interest in the possibilities presented by so-called “big dataset science”—the act of pooling together huge amounts of data in order to generate greater statistical power. She traced a set of disciplines—genetics, epigenetics, proteomics, brain imaging, clinical data, and systems biology—and said that the NIH’s Working Group on Data and Informatics  was seeking systematic ways of integrating and analyzing large biomedical datasets in these crucial areas.

As for treatment, the current emphasis is on stimulants. Volkow said that work continues on finding reliable antagonist drugs to combat the dopamine disruptions promoted by active drug abuse. She suggested that work on buspirone, the D3 receptor antagonist and partial serotonin 5HT agonist used to treat generalized anxiety disorder, has shown that it may reduce cocaine self-administration in rhesus monkeys. This would be of considerable clinical interest, since addiction medicine presently has no effective drug treatments to offer for stimulants like cocaine and methamphetamine. A large clinical study now underway is showing that buspirone blocked D3 receptors in monkey brains in a way that reduced their interest in cocaine.

And she referred to the failed promise of NicVax, the short-lived vaccine for cigarette addiction. The treatment “failed to meet the primary endpoint in Phase II trials.” In other words, it flunked out. Only 30% of addicted smokers developed sufficient antibodies from NicVax to do them any good. But she cited new research on an alternative approach to vaccines, including a new cocaine vaccine (dAd5GNE) shown to be effective in reducing cocaine addiction-related behaviors in rats through the long-term blockade of dopamine transporters.

In a related approach to producing a reliable anti-cocaine antibody, researchers in the Department of Genetic Medicine at Weill Cornell Medical College went to work on “an adeno-associated virus (AAV) gene transfer vector as the delivery vehicle to persistently express an anti-cocaine monoclonal antibody in vivo, which would sequester cocaine in the blood, preventing access to cognate receptors in the brain.” An AAV is a small virus that is infectious but not pathogenic in humans. You might have it right now, but wouldn’t know it, since AAV doesn’t cause disease. So, the researchers used an AAV to build a transporter mechanism for their monoclonal antibody, GNC92H2. In mice, the result was “persistent serum levels of high-affinity, cocaine-specific antibodies that sequestered intravenously administered cocaine in the blood.”

And finally, while the name is still up in the air, a new national institute combining the study of alcohol and the study of all other addictive drugs will follow after final recommendations submitted to NIH Director by year’s end. Volkow briefly laid out the timeline of the merger for the assembled scientists. Call it the Institute for Substance Use Disorders, or the Institute for Addiction Disorders, or the National Institute of Substance Abuse, but whatever the eventual name, it will be fully operational by late 2013, or at least that’s the plan—and Nora Volkow, the current director of the NIDA, which will merge with, or rather absorb, the National Institute on Alcohol Abuse and Alcoholism (NIAAA), won’t be its director (See "NIH Turf Wars"). Whether that’s good or bad is the subject of much debate, but the project marches on, and seems sensible in the end.

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