生物谷報道：1月21日在PNAS（在線版）上公布的一項研究結果表明,，用基因療法治療小鼠的慢性疼痛,，可以達到3個月無疼痛癥狀的效果。
注射的基因能夠讓小鼠在脊髓周圍的神經(jīng)細胞釋放出一種天然的鎮(zhèn)痛藥,，即內啡肽,。研究人員希望該治療方法能夠用于治療急性或慢性疼痛的病人，讓他們不用再忍受阿片止痛藥所帶來的衰弱,。類阿片受體拮抗藥是目前市場上廣泛使用,、全身起效的止痛藥。
紐約西奈山醫(yī)學院（Mount Sinai School of Medicine ）的副教授Andreas Beutler表示,，由于療效差或不能忍受的副作用,，如極端嗜睡、精神混濁并有幻覺,，現(xiàn)有的治療方法往往無法讓慢性疼痛患者滿意,。
Beutler指出，在某些情況下,，副作用限制了使用止痛藥的劑量,。有些病人寧愿忍受一些疼痛也不愿好得更徹底。
有針對性的基因治療可能會避免與阿片止痛藥（如嗎啡）相關的有害副作用,。
在這個實驗中，研究人員將原-乙-內啡肽（prepro-b-endorphin）基因包裝到一個失活的感冒病毒中,，再通過腰椎穿刺或脊椎穿剌將其注射到小鼠的脊髓,。接下來超過三個月的時間,，小鼠的神經(jīng)性疼痛都消失了。
這種治療方法仍處于初步測試階段,，但如果能證實它對人類是安全和有效的,，那么它將極大幫助病人避免現(xiàn)有止痛藥物難以忍受的副作用，以及幫助使用現(xiàn)有藥物無法緩解的病人,。
Beutler說,，晚期癌癥病人也是其中潛在的受益者。
生物谷推薦英文原文：
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
