Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury
Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury
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全身给予木糖基转移酶 1 mRNA 脱氧核酶可促进脊髓挫伤后的恢复
DOI：
10.1016/j.expneurol.2012.06.006
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发表时间：
2012
影响因子：
5.3
通讯作者：
Grimpe B
中科院分区：
文献类型：
--
作者：
Oudega M;Chao OY;Avison DL;Bronson RT;Buchser WJ;Hurtado A;Grimpe B
脊髓损伤后，瘢痕组织中具有生长抑制性糖胺聚糖（GAG-）侧链的蛋白聚糖限制了自发性轴突发芽/再生。减少瘢痕相关抑制的干预措施促进轴突生长反应，并可能促进基于可塑性的脊髓修复。木糖基转移酶-1（XT-1）是启动GAG链形成的酶。我们研究了静脉注射脱氧核酶（DNA酶）到XT-1 mRNA（DNAXT-1as）是否会引起可塑性后，在成年大鼠脊髓的临床相关挫伤。我们的数据表明，全身DNAXT-1as管理导致的感觉运动功能和神经元轴突的存在尾侧损伤的显着增加。DNAXT 1as治疗没有引起病理学或毒理学副作用。重要的是，静脉注射DNAXT-1as不会加重挫伤引起的神经性疼痛。总的来说，我们的数据表明，DNAXT-1as是一种安全的神经治疗剂，有望成为旨在改善脊髓损伤患者生活质量的治疗方法的组成部分。
After spinal cord injury, proteoglycans with growth-inhibitory glycosaminoglycan (GAG-) side chains in scar tissue limit spontaneous axonal sprouting/regeneration. Interventions that reduce scar-related inhibition facilitate an axonal growth response and possibly plasticity-based spinal cord repair. Xylosyltransferase-1 (XT-1) is the enzyme that initiates GAG-chain formation. We investigated whether intravenous administration of a deoxyribozyme (DNA enzyme) to XT-1 mRNA (DNAXT-1as) would elicit plasticity after a clinically relevant contusion of the spinal cord in adult rats. Our data showed that systemic DNAXT-1as administration resulted in a significant increase in sensorimotor function and serotonergic axon presence caudal to the injury. DNAXT1as treatment did not cause pathological or toxicological side effects. Importantly, intravenous delivery of DNAXT-1as did not exacerbate contusion-induced neuropathic pain. Collectively, our data demonstrate that DNAXT-1as is a safe neurotherapeutic, which holds promise to become an integral component of therapies that aim to improve the quality of life of persons with spinal cord injury.
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影响因子：
5.3
作者：
Cameron, AA;Smith, GM;Rabchevsky, AG
通讯作者：
Rabchevsky, AG
影响因子：
5.3
作者：
Jones, LL;Margolis, RU;Tuszynski, MH
通讯作者：
Tuszynski, MH
影响因子：
25
作者：
Thallmair, M;Metz, GAS;Schwab, ME
通讯作者：
Schwab, ME
影响因子：
5.3
作者：
Bruce, JC;Oatway, MA;Weaver, LC
通讯作者：
Weaver, LC
影响因子：
3.4
作者：
Raineteau, O;Z'Graggen, WJ;Schwab, ME
通讯作者：
Schwab, ME