New paradigms for the treatment of lysosomal storage diseases: targeting the endocannabinoid system as a therapeutic strategy.
New paradigms for the treatment of lysosomal storage diseases: targeting the endocannabinoid system as a therapeutic strategy.
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DOI：
10.1186/s13023-021-01779-4
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发表时间：
2021-03-25
影响因子：
3.7
通讯作者：
Simonaro CM
中科院分区：
文献类型：
--
作者：
Schuchman EH;Ledesma MD;Simonaro CM
在过去的三十年中，溶酶体贮积病已成为罕见疾病治疗开发的模型。尽管这些努力取得了巨大成功，但仍然存在重大挑战。例如，目前近三分之二的溶酶体疾病尚未获得批准治疗，并且现有药物对中枢神经系统的影响有限。此外，这些疗法的成本非常高，部分原因是药物开发集中于“单次打击”方法，即一种药物治疗一种疾病。为了克服这些障碍，研究人员开始专注于定义溶酶体疾病的常见疾病机制，特别是中枢神经系统的疾病机制，希望找到可用于多种溶酶体疾病而不是单一疾病的药物。考虑到这一概念，本文回顾了一种针对溶酶体贮积病的新的潜在治疗方法，其重点是调节内源性大麻素系统。我们简要介绍了溶酶体贮积病和内源性大麻素系统，然后简要回顾了支持这一概念的数据。
Over the past three decades the lysosomal storage diseases have served as model for rare disease treatment development. While these efforts have led to considerable success, important challenges remain. For example, no treatments are currently approved for nearly two thirds of all lysosomal diseases, and there is limited impact of the existing drugs on the central nervous system. In addition, the costs of these therapies are extremely high, in part due to the fact that drug development has focused on a “single hit” approach – i.e., one drug for one disease. To overcome these obstacles researchers have begun to focus on defining common disease mechanisms in the lysosomal diseases, particularly in the central nervous system, with the hope of identifying drugs that might be used in several lysosomal diseases rather than an individual disease. With this concept in mind, herein we review a new potential treatment approach for the lysosomal storage diseases that focuses on modulation of the endocannabinoid system. We provide a short introduction to lysosomal storage diseases and the endocannabinoid system, followed by a brief review of data supporting this concept.