Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses
Current and Emerging Treatment Strategies for Neuronal Ceroid Lipofuscinoses
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DOI：
10.1007/s40263-019-00620-8
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发表时间：
2019-04-01
期刊：
影响因子：
6
通讯作者：
Storch, Stephan
中科院分区：
文献类型：
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作者：
Kohlschuetter, Alfried;Schulz, Angela;Storch, Stephan
神经性蜡样脂褐素病包括一组由至少13个不同基因突变引起的神经退行性溶酶体储存障碍，主要影响儿童或年轻人的大脑和视网膜。这些疾病的特征是痴呆、癫痫、视力丧失、运动障碍和过早死亡的进行性神经恶化。虽然目前正在探索各种治疗策略作为这些致命疾病的治疗选择，但目前只有一种临床批准的药物被证明能有效减缓一种特定形式的神经元类脂褐质脂褐素沉着症的进展，CLN2病(一种注入CLN2病患者脑室的溶酶体酶)。治疗其他形式的神经性蜡样脂褐素沉着症的治疗方法包括给予免疫抑制剂以对抗与神经变性相关的神经炎症、使用各种小分子、干细胞治疗和基因治疗。未来旨在开发神经元蜡样脂褐素病治疗方法的一个重要方面是需要有效地减轻大脑和视网膜中的神经退化的治疗方法。
The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epilepsy, loss of vision, motor disturbances, and early death. While various therapeutic strategies are currently being explored as treatment options for these fatal disorders, there is presently only one clinically approved drug that has been shown to effectively attenuate the progression of a specific form of neuronal ceroid lipofuscinosis, CLN2 disease (cerliponase alfa, a lysosomal enzyme infused into the brain ventricles of patients with CLN2 disease). Therapeutic approaches for the treatment of other forms of neuronal ceroid lipofuscinosis include the administration of immunosuppressive agents to antagonize neuroinflammation associated with neurodegeneration, the use of various small molecules, stem cell therapy, and gene therapy. An important aspect of future work aimed at developing therapies for neuronal ceroid lipofuscinoses is the need for treatments that effectively attenuate neurodegeneration in both the brain and the retina.