Neurofilament Light Chain in Amyotrophic Lateral Sclerosis

Overview

This study assesses the performance of serum neurofilament light chain (sNfL) in amyotrophic lateral sclerosis (ALS) in a wide range of disease courses, in terms of ALS progression, disease duration, and tracheostomy invasive ventilation (TIV). The aim of the research project is to investigate the correlation between NfL serum concentration and the natural course of the disease, the ALS progression rate, and specific phenotypes of ALS. Furthermore, the performance of NfL as a therapeutic biomarker will be studied. A systematic analysis of the NfL serum concentration in a cohort of 3,000 ALS patients using the Single Molecule Analysis method (SIMOA) will be performed. This analysis is carried out as a multi-center study.

The aim of this study is to investigate the correlation between the NfL serum concentration and the natural course of the disease, the ALS progression rate as measured by the ALS functional rating scale (ALSFRS-R), and specific phenotypes of ALS. The results of the study will contribute to the assessment of disease progression and the prognosis making of ALS. Furthermore, the performance of NfL as a therapeutic marker of ALS medicines and non-pharmacologic treatment options will be investigated. A systematic analysis of the NfL serum concentration in an extended cohort of ALS patients using the Single Molecule Analysis method (SIMOA) will be performed. Research objectives comprise: * Correlation of NfL with disease progression, including duration of ALS disease * Correlation of NfL with the course of ALS (classic ALS or variants in the motor neuron involvement or the regional propagation patterns) * Correlation of NfL with the progression rate of ALS Cohorts on phenotypic variants: The clinical phenotype of ALS will be differentiated according to the motor neuron involvement or regional propagation patterns of disease onset and clinical course. ALS variants in relation to motor neuron involvement: * Typical ALS: clinical features for an affection of the 1st and 2nd motor neurons are present * Progressive muscular atrophy (PMA): only clinical features for an affection of the 2nd motor neuron are present * Spastic ALS: predominantly clinical features for an affection of the 1st motor neuron and fewer signs of an affection of the 2nd motor neuron * Primary lateral sclerosis (PLS): only clinical features for an affection of the 1st motor neuron are present ALS variants in regional propagation patterns: * Typical form: paresis of the upper or lower extremities or the bulbar region as well as the spread of the paresis to other regions * Flail arm syndrome: primary and dominant paresis of the upper extremities and little or delayed spread of the paresis to other regions * Flail leg syndrome: primary and dominant paresis of the lower extremities and little or delayed spread of the paresis to other regions * Axial ALS: primary and dominant paresis of the trunk muscles and minor or delayed spread of the paresis to other regions * Progressive bulbar paralysis: primary and dominant paresis in the bulbar region and slight or delayed spread of the paresis to other regions