Analysis of Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients: Reduction in Alpha-1-antitrypsin and Increase in IL-23

Abstract

Amyotrophic lateral sclerosis (ALS, Lou Gehrig’s disease) is a devastating incurable disease that involves motor neuron degeneration, stimulation of immune cells and increased inflammatory mediators in the nervous system. Alpha-1-antitrypsin (AAT) and IL-23 are immuno-modulatory/anti-inflammatory proteins involved in controlling inflammation-related pathologies. The present study determines AAT and IL-23 levels in the cerebrospinal fluid (CSF) of newly diagnosed ALS patients and age-matched controls. AAT levels in CSF of ALS patients were significantly reduced by 45% (21.4µg/ml) as compared to the control group (mean 38.8µg/ml, p=0.013). The pro-inflammatory cytokine IL-23 was significantly increased by 30.8% in CSF of ALS patients (1647pg/ml) in comparison to the controls (1259pg/ml, p=0.012). Linear regression analysis revealed a negative correlation coefficient (r=-0.543) of the two measured parameters (p=0.036). The notion of neuroinflammatory process occurring in ALS patients is further supported by the present findings showing reduction in the anti-inflammatory protein AAT and elevation in the pro-inflammatory cytokine IL-23 in CSF of ALS patients. Increasing AAT levels in the patients' nervous system, particularly via intranasal administration, should be considered as a potential therapeutic approach for ALS treatment.