Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial
Gene therapy for mitochondrial diseases: Leber Hereditary Optic Neuropathy as the first candidate for a clinical trial
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DOI：
10.1016/j.crvi.2013.11.011
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发表时间：
2014-03-01
影响因子：
2
通讯作者：
Corral-Debrinski, Marisol
中科院分区：
文献类型：
--
作者：
Cwerman-Thibault, Helene;Augustin, Sebastien;Corral-Debrinski, Marisol
线粒体疾病在大多数医学学科中不能再被忽视；事实上，他们的最低估计患病率高于每5000个新生儿中有1个。尽管在过去的25年里，在鉴定导致线粒体病理的基因突变方面取得了进展，但在有效治疗方面进展缓慢。眼受累是线粒体疾病的常见特征，与视网膜神经元丧失和视神经萎缩引起的严重和不可逆的视力障碍相对应。有趣的是，自2007年以来，三项针对由RPE65突变引起的Leber先天性黑朦的临床试验正在进行中。总的来说，已经证明了在成人和年轻患者中使用眼腺相关病毒的可行性和安全性以及持续的视觉功能改善。RPE65基因替代疗法的成功为开发类似的方法治疗广泛的眼部疾病开辟了道路，包括那些线粒体病因，如Leber遗传性视神经病变（LHON）。(c) 2013年法国科学院。Elsevier Masson SAS出版。版权所有。
Mitochondrial disorders cannot be ignored anymore in most medical disciplines; indeed their minimum estimated prevalence is superior to 1 in 5000 births. Despite the progress made in the last 25 years on the identification of gene mutations causing mitochondrial pathologies, only slow progress was made towards their effective treatments. Ocular involvement is a frequent feature in mitochondrial diseases and corresponds to severe and irreversible visual handicap due to retinal neuron loss and optic atrophy. Interestingly, three clinical trials for Leber Congenital Amaurosis due to RPE65 mutations are ongoing since 2007. Overall, the feasibility and safety of ocular Adeno-Associated Virus delivery in adult and younger patients and consistent visual function improvements have been demonstrated. The success of gene-replacement therapy for RPE65 opens the way for the development of similar approaches for a broad range of eye disorders, including those with mitochondrial etiology such as Leber Hereditary Optic Neuropathy (LHON). (c) 2013 Academie des sciences. Published by Elsevier Masson SAS. All rights reserved.