病毒载体介导的谷氨酸脱羧酶基因转移治疗慢性疼痛:文献综述。
Viral Vector-Mediated Gene Transfer of Glutamic Acid Decarboxylase for Chronic Pain Treatment: A Literature Review.
机构信息
Department of Anesthesiology, University of Miami Miller School of Medicine, Miami, Florida.
Department of Surgery, University of Miami Miller School of Medicine, Miami, Florida.
出版信息
Hum Gene Ther. 2020 Apr;31(7-8):405-414. doi: 10.1089/hum.2019.359. Epub 2020 Mar 24.
Chronic pain is long-lasting nociceptive state, impairing the patient's quality of life. Existing analgesics are generally not effective in the treatment of chronic pain, some of which such as opioids have the risk of tolerance/dependence and overdose death with higher daily opioid doses for increasing analgesic effect. Opioid use disorders have already reached an epidemic level in the United States; therefore, nonopioid analgesic approach and/or use of nonpharmacologic interventions will be employed with increasing frequency. Viral vector-mediated gene therapy is promising in clinical trials in the nervous system diseases. Glutamic acid decarboxylase (GAD) enzyme, a key enzyme in biosynthesis of γ-aminobutyric acid (GABA), plays an important role in analgesic mechanism. In the literature review, we used PubMed and bioRxiv to search the studies, and the eligible criteria include (1) article written in English, (2) use of viral vectors expressing GAD67 or GAD65, and (3) preclinical pain models. We identified 13 eligible original research articles, in which the pain models include nerve injury, HIV-related pain, painful diabetic neuropathy, and formalin test. GAD expressed by the viral vectors from all the reports produced antinociceptive effects. Restoring GABA systems is a promising therapeutic strategy for chronic pain, which provides evidence for the clinical trial of gene therapy for pain in the near future.
慢性疼痛是一种长期的伤害感受性状态,会损害患者的生活质量。现有的镇痛药通常在治疗慢性疼痛方面效果不佳,其中一些药物,如阿片类药物,存在耐受/依赖的风险,并且随着每日阿片类药物剂量的增加以提高镇痛效果,存在过量死亡的风险。阿片类药物使用障碍在美国已经达到流行水平;因此,非阿片类镇痛药方法和/或非药物干预的使用频率将越来越高。病毒载体介导的基因治疗在神经系统疾病的临床试验中很有前途。谷氨酸脱羧酶(GAD)酶是γ-氨基丁酸(GABA)生物合成的关键酶,在镇痛机制中发挥重要作用。在文献综述中,我们使用 PubMed 和 bioRxiv 搜索了研究,合格标准包括(1)用英语撰写的文章,(2)使用表达 GAD67 或 GAD65 的病毒载体,(3)使用临床前疼痛模型。我们确定了 13 篇合格的原始研究文章,其中疼痛模型包括神经损伤、HIV 相关疼痛、痛性糖尿病性神经病和福尔马林试验。所有报告中病毒载体表达的 GAD 都产生了镇痛作用。恢复 GABA 系统是治疗慢性疼痛的一种有前途的治疗策略,为基因治疗在不久的将来治疗疼痛提供了证据。