WP3 extends the clinical data in WP1 with standardized quantification of brain (MRI; upper motor neuron) and spinal cord (MUNIX; lower motor neuron) motor neuron involvement, the hallmarks of ALS. It aims to develop both techniques as widely applicable surrogate markers of disease stage and progression and as markers of therapeutic response in future drug trials. Acquisition of longitudinal MRI and MUNIX data along with other biomarkers will help to understand critical stages of upper and lower motor neuron demise. Thus, WP3 will complement WP1 and WP2 by developing quantitative markers of ALS-related tissue damage. These markers will be included in standardized ALS patient datasets, and will be available for scientific interrogation within the wider neurodegeneration field.
MUNIX measurements require standard electrophysiological equipment and validated SOPs exist, but investigator training is essential to establish cross-centre reliability. Thus, to implement optimization and harmonization, MUNIX demands analysis of factors influencing test-retest reliability across centres, a task which is performed by WP3b.