Edelmann Mariola J, Maegawa Gustavo H B
Department of Microbiology and Cell Science, The University of Florida's Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL, United States.
Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, United States.
Front Mol Biosci. 2020 Nov 12;7:559804. doi: 10.3389/fmolb.2020.559804. eCollection 2020.
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.
在过去几十年中，已经开发出几种治疗方法，并迅速应用于许多患有溶酶体贮积症（LSDs）的患者。溶酶体贮积症是一种先天性细胞器疾病，由于溶酶体内未降解的大分子逐渐积累，临床表现广泛。这些病症各自罕见，但总体发病率在每2315至7700例活产中有1例。大多数溶酶体贮积症表现为神经症状或体征，包括发育迟缓、癫痫发作、肢端感觉异常、肌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，其特征是神经症状进展细微且缓慢。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疗法实现中枢神经系统（CNS）并治疗这些病症中普遍存在的神经问题的重大障碍。为了规避这一限制，已经开发出几种策略以使治疗剂进入中枢神经系统。本叙述将概述目前正在开发的渗透血脑屏障的治疗策略，并解决对治疗这些遗传性溶酶体疾病中普遍存在的进行性神经表现的未满足需求。
