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运动神经元病的未来:挑战在于基因。

The future of motor neuron disease: the challenge is in the genes.

作者信息

Veldink Jan H, Van den Berg Leonard H, Wokke John H J

机构信息

Department of Neurology, G.03.228, University Medical Center Utrecht, P. O. Box 85500, 3508 GA Utrecht, The Netherlands.

出版信息

J Neurol. 2004 Apr;251(4):491-500. doi: 10.1007/s00415-004-0322-6.

Abstract

Adult-onset motor neuron disease (MND) includes sporadic and familial forms of amyotrophic lateral sclerosis (ALS), lower motor neuron disease including progressive and segmental spinal muscular atrophy (LMND) and primary lateral sclerosis (PLS). ALS/MND can be considered to be a spectrum of neurodegenerative diseases characterised by a preferential degeneration of upper and/or lower motor neurons. ALS and LMND have a complex multifactorial aetiology and a large clinical variability. This combination warrants an increasing genomics approach in future research. Genomics is the structural and functional study of genomes--i. e. the complete set of chromosomes and the genes they contain. Several methods may help to understand gene functions, and every method has led to its own "omics". The study of the complex relationship between on the one hand genomics data, transcriptomics data, proteomics data, and interactomics data and on the other hand the phenotype, is called "phenomics". In phenomics, the extensive and detailed phenotyping by the clinician is a prerequisite for meaningful associations. As a consequence, in ALS/MND clinicians have the task to agree about different clinical subtypes in order to make these associations and hence to gain further insight into the complex pathogenesis and identification of diagnostic markers in ALS/MND. Also, several new approaches in the treatment of ALS/MND are here discussed, including the viral delivery of protective compounds, RNA-interference, and stem cell therapy. Further, we argue that a future challenge is to allow for patients to have early access to multidisciplinary centres with specialist knowledge of ALS/MND. These centres can apply specific models of care for people with ALS/MND, but must be designed in a patient-centred format. Ultimately, these models should be assessed according to their outcomes.

摘要

成人起病的运动神经元病(MND)包括散发性和家族性肌萎缩侧索硬化症(ALS)、包括进行性和节段性脊髓性肌萎缩症(LMND)以及原发性侧索硬化症(PLS)在内的下运动神经元病。ALS/MND可被视为一系列神经退行性疾病,其特征是上运动神经元和/或下运动神经元优先发生变性。ALS和LMND具有复杂的多因素病因,临床变异性很大。这种情况使得在未来研究中越来越需要采用基因组学方法。基因组学是对基因组的结构和功能研究——即全套染色体及其所含基因。有几种方法可能有助于理解基因功能,每种方法都催生了其自身的“组学”。研究一方面基因组学数据、转录组学数据、蛋白质组学数据和相互作用组学数据与另一方面表型之间的复杂关系,被称为“表型组学”。在表型组学中,临床医生进行广泛而详细的表型分析是建立有意义关联的先决条件。因此,在ALS/MND中,临床医生的任务是就不同的临床亚型达成共识,以便建立这些关联,从而进一步深入了解ALS/MND的复杂发病机制并识别诊断标志物。此外,本文还讨论了ALS/MND治疗中的几种新方法,包括保护性化合物的病毒递送、RNA干扰和干细胞疗法。此外,我们认为未来的一个挑战是让患者能够尽早进入具备ALS/MND专业知识的多学科中心。这些中心可以为ALS/MND患者应用特定的护理模式,但必须以患者为中心进行设计。最终,这些模式应根据其结果进行评估。

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