生物谷报道：1月21日在PNAS（在线版）上公布的一项研究结果表明，用基因疗法治疗小鼠的慢性疼痛，可以达到3个月无疼痛症状的效果。
注射的基因能够让小鼠在脊髓周围的神经细胞释放出一种天然的镇痛药，即内啡肽。研究人员希望该治疗方法能够用于治疗急性或慢性疼痛的病人，让他们不用再忍受阿片止痛药所带来的衰弱。类阿片受体拮抗药是目前市场上广泛使用、全身起效的止痛药。
纽约西奈山医学院（Mount Sinai School of Medicine ）的副教授Andreas Beutler表示，由于疗效差或不能忍受的副作用，如极端嗜睡、精神混浊并有幻觉，现有的治疗方法往往无法让慢性疼痛患者满意。
Beutler指出，在某些情况下，副作用限制了使用止痛药的剂量。有些病人宁愿忍受一些疼痛也不愿好得更彻底。
有针对性的基因治疗可能会避免与阿片止痛药（如吗啡）相关的有害副作用。
在这个实验中，研究人员将原-乙-内啡肽（prepro-b-endorphin）基因包装到一个失活的感冒病毒中，再通过腰椎穿刺或脊椎穿剌将其注射到小鼠的脊髓。接下来超过三个月的时间，小鼠的神经性疼痛都消失了。
这种治疗方法仍处于初步测试阶段，但如果能证实它对人类是安全和有效的，那么它将极大帮助病人避免现有止痛药物难以忍受的副作用，以及帮助使用现有药物无法缓解的病人。
Beutler说，晚期癌症病人也是其中潜在的受益者。
生物谷推荐英文原文：
Published online before print January 22, 2008, 10.1073/pnas.0708003105
PNAS | January 22, 2008 | vol. 105 | no. 3 | 1055-1060
BIOLOGICAL SCIENCES / NEUROSCIENCE
Sensory neuron targeting by self-complementary AAV8 via lumbar puncture for chronic pain
Benjamin Storek, Matthias Reinhardt, Cheng Wang, William G. M. Janssen, Nina M. Harder, Michaela S. Banck, John H. Morrison, and Andreas S. Beutler*
Departments of Medicine and Neuroscience, Mount Sinai School of Medicine, New York, NY 10029
Edited by Fred H. Gage, Salk Institute for Biological Studies, San Diego, CA, and approved November 27, 2007 (received for review August 24, 2007)
Lumbar puncture (LP) is an attractive route to deliver drugs to the nervous system because it is a safe bedside procedure. Its use for gene therapy has been complicated by poor vector performance and failure to target neurons. Here we report highly effective gene transfer to the primary sensory neurons of the dorsal root ganglia (DRGs) with self-complementary recombinant adeno-associated virus serotype 8 (sc-rAAV8) modeling an LP. Transgene expression was selective for these neurons outlining their cell bodies in the DRGs and their axons projecting into the spinal cord. Immunohistochemical studies demonstrated transduction of cells positive for the nociceptive neuron marker vanilloid receptor subtype 1, the small peptidergic neuron markers substance P and calcitonin gene-related peptide, and the nonpeptidergic neuron marker griffonia simplicifolia isolectin B4. We tested the efficacy of the approach in a rat model of chronic neuropathic pain. A single administration of sc-rAAV8 expressing the analgesic gene prepro-β-endorphin (ppβEP) led to significant (P < 0.0001) reversal of mechanical allodynia for 3 months. The antiallodynic effect could be reversed by the µ-opioid antagonist naloxone 4 months after gene transfer (P < 0.001). Testing of an alternative nonopioid analgesic gene, IL-10, alone or in combination with ppβEP was equally effective (P < 0.0001). All aspects of the procedure, such as the use of an atraumatic injection technique, isotonic diluent, a low-infusion pressure, and a small injection volume, are consistent with clinical practice of intrathecal drug use. Therefore, gene transfer by LP may be suitable for developing gene therapy-based treatments for chronic pain.
adeno-associated virus | dorsal root ganglion | gene therapy | β-endorphin | IL-10
