CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.
CNS-Targeting Therapies for Lysosomal Storage Diseases: Current Advances and Challenges.
复制标题
DOI：
10.3389/fmolb.2020.559804
复制
发表时间：
2020
影响因子：
5
通讯作者：
Maegawa GHB
中科院分区：
文献类型：
--
作者：
Edelmann MJ;Maegawa GHB
在过去的几十年中，已经开发了几种治疗方法，并迅速用于许多患有溶酶体贮积症（LSD）的患者，LSD是一种先天性细胞器疾病，具有继发于溶酶体内未降解大分子进行性积累的广泛临床表现。这些疾病个别罕见，但总体而言，其发病率从1/2，315到7，700活产不等。大多数LSD表现为神经系统症状或体征，包括发育迟缓、癫痫发作、肢端感觉异常、运动无力和锥体外系体征。慢性和迟发性临床形式处于连续谱的一端，其特征在于神经症状的微妙和缓慢进展。不幸的是，由于其固有的生理特性，血脑屏障（BBB）构成了当前和即将到来的治疗的重大障碍，以实现中枢神经系统（CNS）和治疗在这些条件下如此普遍的神经问题。为了规避这种限制，已经开发了几种策略来使治疗剂到达CNS。该叙述将概述目前正在开发的渗透BBB的治疗策略，并解决进行性神经系统表现的治疗需求，这些表现在这些遗传性溶酶体疾病中非常普遍。
During the past decades, several therapeutic approaches have been developed and made rapidly available for many patients afflicted with lysosomal storage disorders (LSDs), inborn organelle disorders with broad clinical manifestations secondary to the progressive accumulation of undegraded macromolecules within lysosomes. These conditions are individually rare, but, collectively, their incidence ranges from 1 in 2,315 to 7,700 live-births. Most LSDs are manifested by neurological symptoms or signs, including developmental delay, seizures, acroparesthesia, motor weakness, and extrapyramidal signs. The chronic and later-onset clinical forms are at one end of the continuum spectrum and are characterized by a subtle and slow progression of neurological symptoms. Due to its inherent physiological properties, unfortunately, the blood-brain barrier (BBB) constitutes a significant obstacle for current and upcoming therapies to achieve the central nervous system (CNS) and treat neurological problems so prevalent in these conditions. To circumvent this limitation, several strategies have been developed to make the therapeutic agent achieve the CNS. This narrative will provide an overview of current therapeutic strategies under development to permeate the BBB, and address and unmet need for treatment of the progressive neurological manifestations, which are so prevalent in these inherited lysosomal disorders.
登录
查看更多内容
影响因子：
1.9
作者：
Katabuchi AU;Godoy V;Shil P;Moser A;Maegawa GHB
通讯作者：
Maegawa GHB
影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
10
作者：
Cabrera, Ingrid;Abasolo, Ibane;Veciana, Jaume
通讯作者：
Veciana, Jaume
影响因子：
--
作者：
Akbarzadeh A;Rezaei-Sadabady R;Davaran S;Joo SW;Zarghami N;Hanifehpour Y;Samiei M;Kouhi M;Nejati-Koshki K
通讯作者：
Nejati-Koshki K
一种新型葡糖脑苷脂伴侣能降低戈谢病和帕金森病患者 iPSC 培养的多巴胺能神经元中的α-突触核蛋白和糖脂水平
影响因子：
5.3
作者：
Aflaki, Elma;Borger, Daniel K.;Sidransky, Ellen
通讯作者：
Sidransky, Ellen