Chitinases as biomarkers of disease aggressiveness in Amyotrophic lateral sclerosis : perspectives through the D50 progression model

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative condition with no cure. Biomarkers that capture the disease’s clinical heterogeneity are therefore urgently needed. This body of work aimed to characterize the biomarker profile of the chitinases, a group of immunomodulatory enzymes. We used a translational approach combining a clinical cohort and pre-clinical murine models to show that key chitinases (CHIT1, CHI3L1, CHI3L2) are upregulated in the cerebrospinal fluid (CSF) of ALS patients and multiple cellular sources, including glia and neurons, drive this. The novel D50 disease progression model was used to show that extent of this dysregulation is predictive of overall disease aggressiveness, thus highlighting the clinical utility of chitinases.