ALS is characterized by significant genetic, clinical, and biological heterogeneity. The heritability of ALS is approximately 50%, and variants in more than 200 genes have been associated with the disease. Clinical features are highly variable for most variants, likely due to interactions with other modifier genes and environmental factors. Mutations in groups of genes belonging to specific ALS pathomechanisms may be associated with distinct phenotypes, but better correlations with clinical and biomarker profiles are still needed. Clinically, patients show significant variability in disease onset and progression, as well as in motor and cognitive phenotypes. Several clinical, neurophysiological, neuropsychological, and neuroradiological measures have been developed to account for this variability, but neurochemical biomarkers may represent an ideal tool to identify homogeneous patient subgroups. The most extensively studied neurochemical biomarkers in ALS are neurofilaments, which are released from degenerating motor neurons into biological fluids and have diagnostic and prognostic value. Other potential biomarkers of neuronal damage in ALS include tau (associated with shorter survival), UCHL1, and TDP-43 (both elevated in ALS patients). Microglial and astrocytic involvement in ALS pathogenesis can be investigated by measuring MCP-1 and GFAP, respectively. Considering the growing evidence implicating IFN-alpha involvement in ALS pathogenesis, we aim to comprehensively profile cytokines, neuroinflammatory markers, and analytes related to neurodegeneration in the plasma and cerebrospinal fluid (CSF) of clinically characterized ALS patients and matched healthy controls. This study will support the validation of IFN-alpha pathway activation as a therapeutic target and explore its association with disease phenotype and progression. Furthermore, correlations between biomarker levels and available clinical data will provide insights into potential diagnostic and prognostic biomarkers for ALS, thereby facilitating future therapeutic development.
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Profiling of neurodegenerative and inflammatory markers in in ALS plasma and CSF
Timeframe: As it is a retrospective study and only biomarker analyses will take place, we plan to start the analysis in October and conclude it in December 2025.