A paracrine paradigm for in vivo gene therapy in the central nervous system:: Treatment of chronic pain
A paracrine paradigm for in vivo gene therapy in the central nervous system:: Treatment of chronic pain
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DOI：
10.1089/10430349950018238
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发表时间：
1999-05-01
影响因子：
4.2
通讯作者：
Iadarola, MJ
中科院分区：
文献类型：
--
作者：
Finegold, AA;Mannes, AJ;Iadarola, MJ
目前针对中枢神经系统疾病的基因治疗努力的一个局限性是直接注射到神经组织中的载体的分布。在这里，我们通过将基因转移到脊髓周围的脑膜来绕过这个问题，实现了治疗慢性疼痛的体内基因转移范例。治疗载体由重组腺病毒组成，编码一种分泌形式的内源性阿片样β-内啡肽。在持续性疼痛的炎症模型中，将载体注射到脊髓周围的脑脊液(CSF)中，转导脑膜软膜细胞。由此导致的β-内啡肽分泌的增加减轻了炎性痛觉过敏，但对基本的伤害性反应没有影响。这种基因转移治疗疼痛的方法可以推广到神经退行性疾病，其中治疗效果的广泛空间分布是关键。
A limitation of current gene therapy efforts aimed at central nervous system disorders concerns distribution of vectors on direct injection into neural tissue. Here we have circumvented this problem by transferring genes to the meninges surrounding the spinal cord, achieving an in vivo gene transfer paradigm for treating chronic pain. The therapeutic vector consisted of a recombinant adenovirus encoding a secreted form of the potent endogenous opioid beta-endorphin. In an inflammation model of persistent pain, administration of the vector into the cerebrospinal fluid (CSF) surrounding the spinal cord transduced meningeal pia mater cells. The resulting increase in beta-endorphin secretion attenuated inflammatory hyperalgesia, yet had no effect on basal nociceptive responses. This demonstration of a gene transfer approach to pain treatment can be generalized to neurodegenerative disorcers in which broad spatial distribution of therapeutic effect is critical.