Behavioral, Hormonal, Inflammatory, and Metabolic Effects Associated with FGF21-Pathway Activation in an ALS Mouse Model

In amyotrophic lateral sclerosis (ALS), motor neuron degeneration occurs simultaneously with systemic metabolic dysfunction and neuro-inflammation. The fibroblast growth factor 21 (FGF21) plays an important role in the regulation of both phenomena and is a major hormone of energetic homeostasis. In this study, we aimed to determine the relevance of FGF21 pathway stimulation in a male mouse model of ALS (mutated SOD1-G93A mice) by using a pharmacological agonist of FGF21, R1Mab1. Mice (SOD1-WT and mutant SOD1-G93A) were treated with R1Mab1 or vehicle. Longitudinal data about clinical status (motor function, body weight) and biological parameters (including hormonal, immunological, and metabolomics profiles) were collected from the first symptoms to euthanasia at week 20. Multivariate models were performed to identify the main parameters associated with R1Mab1 treatment and to link them with clinical status, and metabolic pathways involving the discriminant metabolites were also determined. A beneficial clinical effect of R1Mab1 was revealed on slow rotarod ( p = 0.032), despite a significant decrease in body weight of ALS mice ( p