Tzeplaeff Laura, Galhoz Ana, Meijs Clara, Caldi Gomes Lucas, Kovac Andrej, Menzel Amrei, Değirmenci Hatice, Alaamel Abir, Kaya Hüseyin Can, Çelik Ali Günalp, Dinçer Sine, Korucuk Meltem, Karaüzüm Sibel Berker, Bayraktar Elif, Çiftçi Vildan, Bilge Uğur, Koç Filiz, Demleitner Antonia F, Buchberger Anne, von Heynitz Ricarda, Gmeiner Vincent, Knellwolf Christina, Mouzouri Mohammed, Wuu Joanne, Başak A Nazli, Andersen Peter Munch, Kohlmayer Florian, Ashton Nicholas J, Kuban Wojciech, Lenz Christof, Rogers Mary-Louise, Zilka Norbert, Corcia Philippe, Lerner Yossef, Weber Markus, Turcanova Koprusakova Monika, Uysal Hilmi, Benatar Michael, Menden Michael P, Lingor Paul
Department of Neurology, Rechts Der Isar Hospital of the Technical University Munich, Munich, Germany.
Department of Computational Health, Helmholtz Munich, Neuherberg, Germany.
Neurol Res Pract. 2025 Aug 19;7(1):56. doi: 10.1186/s42466-025-00417-9.
The median time to diagnosis of amyotrophic lateral sclerosis (ALS) is approximately 12 months after the onset of first symptoms. This diagnostic delay is primarily due to the nonspecific nature of early symptoms and the clinical challenges in differentiating ALS from its mimics. Therefore, the discovery of reliable biomarkers for the early and accurate diagnosis of ALS represents a critical medical need.
A total of 330 participants will be recruited across six international study sites. The cohort will include (1) pre-symptomatic gene mutation carriers, (2) symptomatic individuals up to 12 months after symptom onset with either ALS, ALS mimics, or a pure motor syndrome with yet unclear assignment, and (3) healthy controls. Participants will engage in a one-year longitudinal study, consisting of an initial evaluation at baseline visit and a follow-up visit 12 months later. Assessments will include an environmental and medical history questionnaire, neurological examinations, olfactory testing, cognitive/behavioral evaluations, and the collection of biological samples (serum, plasma, urine, tear fluid, and cerebrospinal fluid). Proteomic, metabolomic, and lipidomic analyses will be performed using mass spectrometry and targeted immunoassays, with all samples processed under standardized protocols. The resulting multimodal dataset will be systematically integrated in an effort to uncover a presymptomatic and early ALS signature. Perspective The premodiALS study aim to identify a clinico-molecular signature characteristic of presymptomatic and early ALS. These findings may have relevance to early diagnosis and future clinical practice for ALS disease.
肌萎缩侧索硬化症（ALS）的中位诊断时间约为首次出现症状后的12个月。这种诊断延迟主要是由于早期症状的非特异性以及将ALS与其模仿疾病区分开来的临床挑战。因此，发现用于ALS早期准确诊断的可靠生物标志物是一项迫切的医学需求。
将在六个国际研究地点招募总共330名参与者。队列将包括（1）症状前基因突变携带者，（2）症状出现后12个月内的有症状个体，包括ALS患者、ALS模仿疾病患者或病因尚不明确的纯运动综合征患者，以及（3）健康对照。参与者将参与一项为期一年的纵向研究，包括在基线访视时进行初始评估以及12个月后的随访。评估将包括环境和病史问卷、神经学检查、嗅觉测试、认知/行为评估以及生物样本（血清、血浆、尿液、泪液和脑脊液）的采集。将使用质谱和靶向免疫测定法进行蛋白质组学、代谢组学和脂质组学分析，所有样本均按照标准化方案进行处理。由此产生的多模态数据集将被系统整合，以努力发现症状前和早期ALS的特征。观点：premodiALS研究旨在识别症状前和早期ALS的临床分子特征。这些发现可能与ALS疾病的早期诊断和未来临床实践相关。
