Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A.
Squalenoyl siRNA PMP22 nanoparticles are effective in treating mouse models of Charcot-Marie-Tooth disease type 1 A.
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DOI：
10.1038/s42003-021-01839-2
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发表时间：
2021-03-09
影响因子：
5.9
通讯作者：
Massaad-Massade L
中科院分区：
文献类型：
--
作者：
Boutary S;Caillaud M;El Madani M;Vallat JM;Loisel-Duwattez J;Rouyer A;Richard L;Gracia C;Urbinati G;Desmaële D;Echaniz-Laguna A;Adams D;Couvreur P;Schumacher M;Massaad C;Massaad-Massade L
腓骨肌萎缩症1A型（CMT 1A）缺乏有效的治疗。我们提供了一种基于与角鲨烯纳米颗粒缀合的siRNA（siRNA PMP 22-SQ NPs）的CMT 1A疗法。它们的施用导致Pmp 22蛋白水平正常化，在具有不同疾病严重程度的两种转基因CMT 1A小鼠模型中恢复运动活性和电生理参数。病理学研究表明，再生的有髓轴突和髓鞘压实，在恢复髓鞘功能的一个主要步骤。坐骨神经Krox 20、Sox 10和神经丝水平的正常化反映了髓鞘和轴突的再生。重要的是，siRNA PMP 22-SQ NP的积极作用持续了三周，并且它们的重新施用导致了完全的功能恢复。除了CMT 1A，我们的研究结果可以被认为是遗传性周围神经病的有效治疗策略。它们为基于siRNA使疾病基因表达正常化的新型精准医学提供了概念证明。Boutary等人描述了与角鲨烯纳米颗粒缀合的基于siRNA的疗法作为使CMT 1A小鼠模型中的PMP 22蛋白水平正常化、恢复运动活性、电生理参数和髓鞘功能的有效方法。这些发现可能有助于开发遗传性周围神经病的治疗策略。
Charcot-Marie-Tooth disease type 1 A (CMT1A) lacks an effective treatment. We provide a therapy for CMT1A, based on siRNA conjugated to squalene nanoparticles (siRNA PMP22-SQ NPs). Their administration resulted in normalization of Pmp22 protein levels, restored locomotor activity and electrophysiological parameters in two transgenic CMT1A mouse models with different severity of the disease. Pathological studies demonstrated the regeneration of myelinated axons and myelin compaction, one major step in restoring function of myelin sheaths. The normalization of sciatic nerve Krox20, Sox10 and neurofilament levels reflected the regeneration of both myelin and axons. Importantly, the positive effects of siRNA PMP22-SQ NPs lasted for three weeks, and their renewed administration resulted in full functional recovery. Beyond CMT1A, our findings can be considered as a potent therapeutic strategy for inherited peripheral neuropathies. They provide the proof of concept for a new precision medicine based on the normalization of disease gene expression by siRNA. Boutary et al. describe siRNA based therapy conjugated with squalene nanoparticles as an efficient approach to normalize PMP22 protein levels, restore locomotor activity, electrophysiological parameters and function of myelin sheath in CMT1A mouse models. These findings could be useful to develop therapeutic strategies for inherited peripheral neuropathies.
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影响因子：
3.7
作者：
Ali HM;Urbinati G;Chapuis H;Desmaele D;Bertrand JR;Couvreur P;Massaad-Massade L
通讯作者：
Massaad-Massade L
影响因子：
13.6
作者：
Feng, Jiao;Lepetre-Mouelhi, Sinda;Couvreur, Patrick
通讯作者：
Couvreur, Patrick
影响因子：
1.8
作者：
Dulsat, C.
通讯作者：
Dulsat, C.
影响因子：
11.2
作者：
Guo J;Wang L;Zhang Y;Wu J;Arpag S;Hu B;Imhof BA;Tian X;Carter BD;Suter U;Li J
通讯作者：
Li J
影响因子：
4.2
作者：
BOUTRY, JM;HAUW, JJ;BARONVANEVERCOOREN, A
通讯作者：
BARONVANEVERCOOREN, A