Fingolimod: A Disease-Modifier Drug in a Mouse Model of Amyotrophic Lateral Sclerosis

• Published in: Neurotherapeutics 2016-10, Vol.13 (4), p.918-927
• Main Authors: Potenza, Rosa Luisa, De Simone, Roberta, Armida, Monica, Mazziotti, Valentina, Pèzzola, Antonella, Popoli, Patrizia, Minghetti, Luisa
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - complications; Amyotrophic Lateral Sclerosis - drug therapy; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Animals; Biomedical and Life Sciences; Biomedicine; Body Weight - drug effects; Body Weight - genetics; Brain - metabolism; Brain - pathology; Cytokines - genetics; Cytokines - metabolism; Disease; Disease Models, Animal; Fingolimod Hydrochloride - pharmacology; Fingolimod Hydrochloride - therapeutic use; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Gene Expression Regulation - drug effects; Gene Expression Regulation - genetics; Genotype & phenotype; Humans; Immunosuppressive Agents - pharmacology; Immunosuppressive Agents - therapeutic use; Kinases; Lymphocytes; Mice; Mice, Inbred C57BL; Mice, Transgenic; Movement Disorders - drug therapy; Movement Disorders - etiology; Multiple sclerosis; Mutation - genetics; Nervous system; Neurobiology; Neurology; Neurosciences; Neurosurgery; Neurotoxicity; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Original; Original Article; Spinal cord; Spinal Cord - drug effects; Spinal Cord - metabolism; Spinal Cord - pathology; Superoxide Dismutase - genetics
• ISSN: 1933-7213; 1878-7479; 1878-7479
• DOI: 10.1007/s13311-016-0462-2

Fingolimod phosphate (FTY720), the first approved oral therapy for multiple sclerosis, primarily acts as an immunomodulator. Its concomitant effects in the central nervous system, however, indicate a potentially broader spectrum of activity in neurodegenerative diseases. In the present study, we investigated the possible effects of fingolimod in a mouse model of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by a strong neuroinflammatory component. Fingolimod (0.1 and 1 mg/kg i.p.) was administered to mSOD1 G93A mice, a well-characterized mouse model of ALS, starting from the onset of motor symptoms to the end stage of the disease. The drug was able to improve the neurological phenotype ( p