Behavioral, Hormonal, Inflammatory, and Metabolic Effects Associated with FGF21-Pathway Activation in an ALS Mouse
J B Delaye1, D Lanznaster2, C Veyrat-Durebex3,2
1Laboratoire de Biochimie et de Biologie Moléculaire, Centre Hospitalier Régional Universitaire de Tours, 2 Bd Tonnellé, 37044, Tours Cedex, France. j.delaye@chu-tours.fr.
Summary
Fibroblast growth factor 21 (FGF21) pathway stimulation showed a mild improvement in motor function for amyotrophic lateral sclerosis (ALS) mice. This treatment also demonstrated anti-inflammatory and metabolic benefits, suggesting FGF21 as a potential therapeutic target for ALS.
Area of Science:
- Neuroscience
- Metabolic research
- Pharmacology
Background:
- Amyotrophic lateral sclerosis (ALS) involves motor neuron degeneration, systemic metabolic dysfunction, and neuro-inflammation.
- Fibroblast growth factor 21 (FGF21) is a key hormone regulating energy homeostasis and influencing metabolic and inflammatory processes.
Purpose of the Study:
- To investigate the therapeutic potential of stimulating the FGF21 pathway in a mouse model of ALS.
- To evaluate the effects of a pharmacological FGF21 agonist, R1Mab1, on clinical and biological parameters in SOD1-G93A mice.
Main Methods:
- Male SOD1-WT and SOD1-G93A mice were treated with R1Mab1 or vehicle.
- Longitudinal data on motor function, body weight, hormonal, immunological, and metabolomics profiles were collected.
- Multivariate models were used to analyze treatment effects and identify associated metabolic pathways.
Main Results:
- R1Mab1 treatment showed a beneficial effect on motor function (slow rotarod performance) in ALS mice.
- Significant decreases in serum levels of TNF-α, MCP-1, and insulin were observed.
- Metabolomics analysis revealed significant pathway alterations, including sphingolipid metabolism and amino acid metabolism, linked to R1Mab1 treatment.
Conclusions:
- Stimulation of the FGF21 pathway with R1Mab1 offers a potential therapeutic strategy for ALS.
- The treatment exhibited a modest improvement in motor function, accompanied by anti-inflammatory and metabolic benefits.
- FGF21 pathway modulation presents a promising avenue for ALS research and treatment development.
