Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.
Moving towards effective therapeutic strategies for Neuronal Ceroid Lipofuscinosis.
复制标题
DOI：
10.1186/s13023-016-0414-2
复制
发表时间：
2016-04-16
影响因子：
3.7
通讯作者：
Weimer JM
中科院分区：
文献类型：
--
作者：
Geraets RD;Koh Sy;Hastings ML;Kielian T;Pearce DA;Weimer JM
神经性蜡样脂褐素病(NCLS)是一种常染色体隐性遗传性神经退行性疾病家族，每年影响全球1：100,000名活产儿。这一疾病家族是由14种不同基因中的一种突变导致的，这些基因具有共同的临床和病理病因。临床上，根据发病年龄，这些疾病可细分为婴儿型、婴儿期晚期、青少年型和成年型。虽然疾病的表型在年龄和表现顺序上可能有所不同，但通常都包括进行性视力恶化和失明、认知障碍、运动障碍和癫痫发作。NCLS的病理特征包括溶酶体中储存物质或类脂的积聚，进行性神经元变性和大量胶质细胞激活。在家庭遗传诊断和咨询方面取得了进展。然而，延缓或阻止疾病进展的综合治疗计划一直难以捉摸。目前的疾病管理主要针对的是控制症状，而不是“治愈”疾病。认识到日益需要透明度和协同努力来推动该领域的发展，本综述将概述目前在临床前和临床试验中正在进行的治疗方法，以治疗不同形式的NCL，并为NCLS开发新的治疗方法提供洞察力。
The Neuronal Ceroid Lipofuscinoses (NCLs) are a family of autosomal recessive neurodegenerative disorders that annually affect 1:100,000 live births worldwide. This family of diseases results from mutations in one of 14 different genes that share common clinical and pathological etiologies. Clinically, the diseases are subcategorized into infantile, late-infantile, juvenile and adult forms based on their age of onset. Though the disease phenotypes may vary in their age and order of presentation, all typically include progressive visual deterioration and blindness, cognitive impairment, motor deficits and seizures. Pathological hallmarks of NCLs include the accumulation of storage material or ceroid in the lysosome, progressive neuronal degeneration and massive glial activation. Advances have been made in genetic diagnosis and counseling for families. However, comprehensive treatment programs that delay or halt disease progression have been elusive. Current disease management is primarily targeted at controlling the symptoms rather than “curing” the disease. Recognizing the growing need for transparency and synergistic efforts to move the field forward, this review will provide an overview of the therapeutic approaches currently being pursued in preclinical and clinical trials to treat different forms of NCL as well as provide insight to novel therapeutic approaches in development for the NCLs.