GLOBAL OPIOID EPIDEMIC: DOOMED TO FAIL WITHOUT GENETICALLY BASED PRECISION ADDICTION MEDICINE (PAM): LESSONS LEARNED FROM AMERICA.

Precision medicine Pub Date : 2017-01-01 Epub Date: 2017-11-18
Kenneth Blum, Edward J Modestino, Marjorie C Gondré-Lewis, Jennifer Neary, David Siwicki, Mary Hauser, Debmalya Barh, Bruce Steinberg, Rajendra D Badgaiyan
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Abstract

It is a reality that globally opioid deaths have soared for men and women of all social, economic status and age from heroin and fentanyl overdoses. Specifically, in the United States, deaths from narcotic overdoses have reached alarming metrics since 2010. In fact, the Fentanyl rise is driven by drug dealers who sell it as heroin or who use it to lace cocaine or to make illegal counterfeit prescription opioids. The President's Commission on the crisis has linked the death toll as equivalent to "September 11th every three weeks." In fact, The U.S. Centre for Disease Control (CDC) released data showing that opioid-related overdoses were up 15% in the first three quarters of 2016 compared to 2015. Various governmental organizations including NIDA, are actively seeking solutions. However, we argue that unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce "dopamine homeostasis" it will fail. We now have evidence that a ten-gene and eleven single nucleotide polymorphism (SNP) panel predicts Addiction Severity Index (ASI) for both alcohol and drugs of abuse (e.g., Opioids). In a large multi-addiction centre study involving seven diverse treatment programs, the genetic addiction risk score (GARS) was shown to have a predictive relationship with ASI-MV derived alcohol (≥ seven alleles), and other drugs (≥ 4 alleles) severity risk scores. In a number of neuroimaging studies, we also display that in both animal (bench) and abstinent Chinese severe heroin-dependent patients (bedside), BOLD dopamine activation across the brain reward circuitry revealed increases in resting state functional connectivity as well volume connectivity. It is also known that published nutrigenomic (coupling gene polymorphisms with altered KB220z) studies reveal improved clinical outcomes related to obesity.

全球阿片类药物流行病:没有基于基因的精确成瘾药物(pam™)注定要失败:从美国吸取的教训。
全球各种社会、经济地位和年龄的男性和女性因过量服用海洛因和芬太尼而死于阿片类药物的人数激增,这是一个现实。具体来说,在美国,自2010年以来,因麻醉药物过量而死亡的人数达到了惊人的水平。事实上,芬太尼的价格上涨是由毒贩推动的,他们把芬太尼当作海洛因出售,或者用它来添加可卡因,或者制造非法的假冒处方阿片类药物。总统危机委员会将死亡人数与“每三周发生一次的911事件”联系起来。事实上,美国疾病控制中心(CDC)发布的数据显示,与2015年相比,2016年前三个季度阿片类药物相关的过量用药增加了15%。包括NIDA在内的各政府机构正在积极寻求解决方案。然而,我们认为,除非科学界将遗传成瘾风险与潜在的精确或个性化药物结合起来,以诱导“多巴胺稳态”,否则它将失败。我们现在有证据表明,10个基因和11个单核苷酸多态性(SNP)小组可以预测酒精和滥用药物(如阿片类药物)的成瘾严重程度指数(ASI)。在一项涉及七种不同治疗方案的大型多成瘾中心研究中,遗传成瘾风险评分(GARS™)显示与ASI-MV衍生酒精(≥7个等位基因)和其他药物(≥4个等位基因)严重程度风险评分具有预测关系。在许多神经影像学研究中,我们还发现,在动物(实验)和戒断的中国严重海洛因依赖患者(床边)中,大脑奖赏回路中的BOLD多巴胺激活显示静息状态功能连通性和体积连通性增加。众所周知,已发表的营养基因组学(将基因多态性与改变的KB220z偶联)研究揭示了与肥胖相关的临床结果的改善。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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