NEWS OF THE DRUG
TREATMENT
COCAINE VACCINE Viruses decorated with anticocaine antibodies mop up cocaine in rat brain
U
NLIKE HEROIN ADDICTION,
which can be treated with methadone, no effective pharmaceutical treatments for cocaine addiction are available. A team at Scripps Research Institute now reports a potential vaccine for cocaine addiction based on bacteria-infecting viruses with anticocaine antibodies on their surfaces. The viruses, known as bacteriophages, are administered to rats through the nose and get into the rats' brains, where the antibodies can sequester cocaine [Proc Natl. Acad. Sci. USA, published online, http://www.pnas. org/cgi/doi/10.1073/pnas.0403 795101}. Other groups previously have worked on developing antibodies for cocaine treatment. A drawback to such antibodies and other protein-based therapeutics is that they act on the cocaine peripherally—outside the central nervous system. Chemistry professor Kim D. Janda and his team modified the viruses so that they display the anticocaine antibody on the viruses' major coat protein (protein-8 or pVIII), which is abundant enough to display many copies—possibly thousands—of the antibody on each virus. The researchers gave rats the viruses by intranasal injection twice a day for three days. They then injected the animals with systemic doses of cocaine for four consecutive days and monitored the rats' behavior. The virus levels dropped off after a couple of weeks, so the vaccine would need to be administered frequently. One behavioral test uses cages crossed by infrared beams. Because cocaine is a stimulant, HTTP://WWW.CEN-ONLINE.ORG
a rat on cocaine "will move around more and break the beams of light,"Janda says. The second test involves observing "sniffing and rearing" behavior, in which a rat will stop and lift itself up on its hind legs. The rats that received the viruses demonstrated fewer of the usual responses to cocaine than the control rats. The antibody-decorated viruses won't be ready for use in humans for quite some time. "I'm not going to lie to you," Janda says. 'We're not going to be in the clinic in the next year or two." In the future, Janda expects that bacteriophages could be used to deliver other types ofproteins as well. "We'd like to move forward and see what happens if we display an enzyme, because an enzyme could have better efficiency" Enzymes could be used
DRUG
ANTIBODY FERRY Single-chain antibody (pink and blue) that binds cocaine is displayed on the pVIII coat of the virus (green).
to treat conditions other than drug addiction. John R. Cashman, director of the Human BioMolecular Research Institute, San Diego, says: "What is particularly striking is the authors' merging of three exciting fields of research—nasal drug delivery, gene/protein delivery, and phage display—to accomplish their goals. The interdisciplinary approach is a real tour de force and shows that even relatively large particles can be delivered to the brain."—CELIA HENRY
DEVELOPMENT
Merck, Vertex To Collaborate On Cancer Drug
C
ontinuing its push into cancer therapeutics, Merck will collaborate with Vertex Pharmaceuticals to develop a Vertex small-molecule drug. The drug, known as VX-680, is an Aurora kinase inhibitor expected to enter Phase I clinical development later this year for the treatment of cancer. Aurora kinases are a family of serine-threonine kinases believed to play multiple roles in the development and progression of cancer. Merck will pay Vertex $20 million up front and an additional $ U million in R&D funding over the next two years. Vertex could eventually receive as much as $350 million in milestone payments, depending on the success of the drug. The deal is another signal of Merck's renewed interest in cancer therapy, after
many years as a minor player in the sector. In February, the company acquired Aton Pharma, a small biotech company that is developing a treatment for cutaneous T-cell lymphoma. The collaboration is also emblematic of Merck's more aggressive use of alliances to develop its drug pipeline, which was hit by two Phase III trial failures in 2003. Other recent Merck deals include an agreement to develop a Bristol-Myers Squibb diabetes treatment and February's alliance with Lundbeck to develop a sleep-disorder drug. For its part, Vertex has been concentrating on antiviral and anti-inflammation products. CEO Joshua Boger says the Merck deal advances a goal of using collaborations to capture more value from Vertex research.— MICHAEL MCCOY
C & E N / J U N E 2 8 , 2004
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