Amyotrophic lateral sclerosis: Evidence for intact hepatocyte growth factor/MET signalling axis

Hepatocyte growth factor (HGF) is a secreted cytokine which is expressed in the central nervous system (CNS) together with its specific receptor MET. Since HGF exerts strong neurotrophic activity including motoneurons, we hav e further analysed whether the HGF/MET axis is defective in patients with a myotrophic lateral sclerosis (ALS). Intrathecal HGF-secretion was measured in cerebrospinal fluid (CSF) from patients with amyotrophic lateral scleros is and in controls without neurological diseases using a specific sandwich immunoassay (ELISA). MET-expression was analysed by immunohistology in spin al cord cross-sections of ALS patients and unaffected controls. The HGF con centrations in CSF were moderately but significantly increased in ALS patie nts compared to healthy controls (580 pg/ml vs 348 pg/ml). MET-protein was detectable in spinal cord motoneurons of patients with ALS as well as unaff ected controls. The data demonstrate that ALS does not show a lack of the t rophic signalling axis, HGF/MET, suggesting that the signalling system itse lf is not affected. The moderate increase in HGF-secretion may represent a compensatory effect.