Archive for December, 2009

Cocaine Vaccine Shows Promise for Treating Addiction

Tuesday, December 29th, 2009

Immunization with an experimental anti-cocaine vaccine resulted in a substantial reduction in cocaine use in 38 percent of vaccinated patients in a clinical trial supported by the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health. The study, published in the October issue of the Archives of General Psychiatry, is the first successful, placebo-controlled demonstration of a vaccine against an illicit drug of abuse.

“The results of this study represent a promising step toward an effective medical treatment for cocaine addiction,” said NIDA Director Dr. Nora Volkow.” Provided that larger follow-up studies confirm its safety and efficacy, this vaccine would offer a valuable new approach to treating cocaine addiction, for which no FDA-approved medication is currently available.”

Like vaccines against infectious diseases such as measles and influenza, the anti-cocaine vaccine stimulates the immune system to produce antibodies. Unlike antibodies against infectious diseases, which destroy or deactivate the disease-causing agents, anti-cocaine antibodies attach themselves to cocaine molecules in the blood, preventing them from passing through the blood-brain barrier. By preventing the drug’s entry into the brain, the vaccine inhibits or blocks the cocaine-induced euphoria.

This study included 115 patients from a methadone maintenance program who were randomly assigned to receive the anti-cocaine vaccine or a placebo (inactive) vaccine. Participants were recruited from a methadone maintenance program because their retention rates are substantially better than programs focused primarily on treatment for cocaine abuse. Participants in both groups received five vaccinations over a 12-week period and were followed for an additional 12 weeks. All participants also took part in weekly relapse-prevention therapy sessions with a trained substance abuse counselor, had their blood tested for antibodies to cocaine, and had their urine tested three times a week for the presence of opioids and cocaine.

Participants differed in the levels of antibodies generated in response to vaccination. Thirty-eight percent attained blood levels of anti-cocaine antibodies thought to be sufficient to block cocaine’s euphoric effects. During weeks 9 to 16 (when antibody levels peaked), these participants had significantly more cocaine-free urines than those who received the placebo or those with active vaccine but low levels of anti-cocaine antibodies. Participants with the highest antibody levels had the greatest reductions in cocaine use. No serious adverse effects were associated with vaccine treatment.

“Fifty-three percent of participants in the high-antibody group were abstinent from cocaine more than half the time during weeks 8 to 20, compared with only 23 percent of participants with lower levels of antibodies,” said Thomas Kosten, M.D., of Baylor College of Medicine in Houston, the study’s principal investigator.

“In this study immunization did not achieve complete abstinence from cocaine use,” added Dr. Kosten. “Previous research has shown, however, that a reduction in use is associated with a significant improvement in cocaine abusers’ social functioning and thus is therapeutically meaningful.”

Dr. Kosten led the study in collaboration with colleagues from Yale University School of Medicine, the Connecticut Veterans Administration (VA) Healthcare System, Baylor College of Medicine, and the Michael E. DeBakey VA Medical Center.

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Gene Duplication Identified in an Uncommon Form of Bone Cancer

Tuesday, December 22nd, 2009

Scientists have discovered that a familial form of a rare bone cancer called chordoma is explained not by typical types of changes or mutations in the sequence of DNA in a gene, but rather by the presence of a second copy of an entire gene. Inherited large structural changes, known as copy number variations (CNVs), have been implicated in some hereditary diseases but have seldom been reported as the underlying basis for a familial cancer. This finding appeared online Oct. 4, 2009, in Nature Genetics and was done by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and their colleagues.

“That an inherited duplication of a gene is responsible for the development of a familial form of cancer is an important finding,” said Rose Yang, Ph.D., NCI, one of the lead authors of the study.

Usual types of gene mutations and gene duplications are permanent changes to the DNA that a person inherits from parents. These changes often alter the expression of the affected gene in ways that lead to cancer and other diseases. The new finding highlights the importance of CNVs, as well as typical specific genetic mutations, in the genetic development of cancer.

Chordoma affects about 1 in every 1 million people in the United States, with about 300 new cases diagnosed each year. Those affected with the disease usually develop a tumor at the base of the skull, or at any point along the spinal column including the tailbone. The growths are thought to arise from remnants of the notochord, an embryonic precursor to the spinal column. There are few effective treatments and no cure for chordoma; many people with the non-familial form of chordoma die within 10 years of diagnosis.

Yang, together with Dilys Parry, Ph.D., also from NCI, and Michael Kelley, M.D., Duke University Medical Center, Durham, N.C., who is a former NCI researcher, based their initial finding on a large family studied by Parry with a history of chordoma that spanned several generations.

Because of the familial nature of this cancer, the researchers searched for a genetic alteration that could help explain the increased risk to family members. Initially they considered possible defects on chromosome 7, but no mutation was found that was shared by all affected relatives. The researchers then conducted further linkage studies, which look for patterns that appear in every affected member of a family, and found six new areas in the genome that warranted further study. The area that looked to be the most promising was on chromosome 6, in a region that contained a gene related to notochord development that is called the T gene or brachyury.

“Brachyury is active in the chordoma cells in many people with this cancer” said Parry, “and because the T gene also regulates the development of the notochord we thought this gene might be a strong candidate for chordoma.” However, no disease-related mutation that altered the DNA sequence of this gene was found.

The scientists then looked for CNVs in the region on chromosome 6 that included the T gene in DNA from seven families (65 people, including 21 chordoma patients) in which at least two blood relatives had the disease. The scientists found that in four of the families, all of those with the disease had a second copy of the T gene. The duplications were not found in the chordoma patients from the other three families or in 100 healthy normal controls. “Chordomas in the three families without T gene duplications may result from mutations of other genes or an as yet unidentified process involving the T gene,” said Yang.

Based on their finding that duplications of the T gene cause an increased risk for chordoma in some families, the scientists suggest that future efforts to identify novel genes for familial cancers may benefit from screening for complex genomic rearrangements in addition to using traditional gene-mapping approaches.

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