Garbuzova-Davis Svitlana, Thomson Avery, Kurien Crupa, Shytle R Douglas, Sanberg Paul R
a Center of Excellence for Aging & Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
b Department of Neurosurgery and Brain Repair , University of South Florida, Morsani College of Medicine , Tampa , FL , USA.
Expert Rev Neurother. 2016 Dec;16(12):1397-1405. doi: 10.1080/14737175.2016.1207530. Epub 2016 Jul 15.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron degeneration in the brain and spinal cord. Treatment development for ALS is complicated by complex underlying disease factors. Areas covered: Numerous tested drug compounds have shown no benefits in ALS patients, although effective in animal models. Discrepant results of pre-clinical animal studies and clinical trials for ALS have primarily been attributed to limitations of ALS animal models for drug-screening studies and methodological inconsistencies in human trials. Current status of pre-clinical and clinical trials in ALS is summarized. Specific blood-CNS barrier damage in ALS patients, as a novel potential reason for the clinical failures in drug therapies, is discussed. Expert commentary: Pathological perivascular collagen IV accumulation, one unique characteristic of barrier damage in ALS patients, could be hindering transport of therapeutics to the CNS. Restoration of B-CNS-B integrity would foster delivery of therapeutics to the CNS.
肌萎缩侧索硬化症（ALS）是一种致命的神经退行性疾病，其特征是大脑和脊髓中的运动神经元退化。ALS复杂的潜在疾病因素使治疗开发变得复杂。涵盖领域：尽管许多经过测试的药物化合物在动物模型中有效，但在ALS患者中并未显示出益处。ALS临床前动物研究和临床试验结果的差异主要归因于用于药物筛选研究的ALS动物模型的局限性以及人体试验中的方法学不一致。总结了ALS临床前和临床试验的现状。讨论了ALS患者中特定的血脑屏障损伤，这是药物治疗临床失败的一个新的潜在原因。专家评论：病理性血管周围IV型胶原蛋白积累是ALS患者屏障损伤的一个独特特征，可能会阻碍治疗药物向中枢神经系统的转运。恢复血脑屏障的完整性将促进治疗药物向中枢神经系统的递送。
