Information from Lay-Language Summaries is Embargoed Until the Conclusion of the Scientific Presentation
119—Addiction Treatment and Genetics: Translational Studies
Sunday, November 10, 2013, 8:00 am - 11:30 am
119.14: Gender and genetics interact to modulate response to cocaine vaccine
C. J. SPELLICY1,2, S. C. HAMON3, M. J. HARDING1,2, *C. D. VERRICO1, T. R. KOSTEN1,2, D. A. NIELSEN1,2; 1Menninger Dept. of Psychiatry & Behavioral Sci., Baylor Col. of Med., Houston, TX; 2Michael E. DeBakey V.A. Med. Ctr., Houston, TX; 3Lab. of Statistical Genet., The Rockefeller Univ., New York, NY
Abstract Body: The aim of this study is to identify genetic variants that differentially modulate response to treatment with cocaine vaccine between male and female patients. Sixty-six cocaine-dependent (CD) participants received cocaine vaccine treatment or placebo via intramuscular injection at 0, 2, 4, 8 and 12 weeks, along with cognitive behavioral therapy. Urine was collected three times weekly and screened for a cocaine metabolite. Treatment efficacy was gauged by change in number of positive urines. DNA from participants was genotyped for the GAD1 rs1978340 and rs769390 variants, and the TPH1 rs1799913 variant using TaqMan assays. Data was analyzed via repeated measures ANOVAs and corrected for population structure. Analyses show that males and females respond differently to cocaine vaccine based on the rs1978340 (p ≤ 0.0001) and rs769390 (p ≤ 0.0001) variants in GAD1, and on the rs1799913 (p = 0.04) variant in TPH1. Specifically, females carrying an A allele of rs1978340 in GAD1, males with an A allele of rs769390 and females with a C allele of rs769390 in GAD1, and men with a G allele in TPH1 exhibited better response to the cocaine vaccine (e.g., fewer cocaine-positive urines) than those participants without these alleles. These results illustrate that differences in genetic makeup and gender may modify the effectiveness of the cocaine vaccine in curbing cocaine use in CD individuals. This knowledge may help to personalize therapy for cocaine dependence based on both gender and genetic profile, therefore increasing the probability of treatment efficacy.
Lay Language Summary: Our research indicates that men and women who are dependent on cocaine may respond differently to treatment with a cocaine vaccine based on their genetic makeup. We recently completed a clinical trial for treating cocaine dependence using a vaccine that stimulates the production of antibodies that bind cocaine as it is introduced to the bloodstream. Individuals who have been treated with this vaccine do not achieve the same ‘high’ and tend to use less cocaine. However, only about half the participants in our study reduced their cocaine use. Therefore, other factors may exist that influence the effectiveness of the cocaine vaccine. We demonstrated that a person’s genetic makeup is one of those factors. Cocaine is one of the most commonly abused drugs in the United States and there is currently no FDA-approved medication with which to treat cocaine dependence. Given the significant economic and interpersonal repercussions of drug abuse, new treatment strategies are sorely needed. In addition, how men and women experience and become addicted to cocaine differs. Our goal is to better understand the brain pathways through which cocaine dependence may develop and persist. By better understanding these pathways, we may improve efficacy of existing treatments and aid in the development of new treatments for cocaine dependence. In this study, we examined the role a person’s genetic makeup plays in the ability to respond to the cocaine vaccine, and whether these responses are different between men and women. Our clinical trial of the cocaine vaccine showed that some individuals responded well to the vaccine and used less cocaine if they made enough antibodies to the drug. We also found that in the ninety-four treatment-seeking participants who completed this clinical trial, individuals with certain genetic backgrounds used less cocaine after vaccine treatment. We tested several genetic variants previously found to be associated with addiction and/or psychiatric disorders. Some of these genetic variants predicted a different treatment response to the cocaine vaccine between women and men. Specifically, women carrying a specific form of the glutamate decarboxylase 1 (GAD1) gene, and males with a different form of this gene used less cocaine when treated with the vaccine than those with other forms of the gene. These results further support findings that men and women experience cocaine differently, and that treatments for cocaine dependence may work differently in men or women based on their genetic makeup. We plan to test additional therapies that may help individuals discontinue the use of cocaine, and to identify genetic components that affect the success of these therapies. In the near future, genetic methods may be used to determine the most appropriate treatments for the delivery of personalized medicine for cocaine dependence.
Neuroscience 2013 (43rd annual meeting of the Society for Neuroscience)Exit