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

Neurotherapeutics. 2016 Oct;13(4):918-927. 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 mSOD1G93A 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 < 0.05) and to extend the survival (p < 0.01) of ALS mice. The beneficial effect of fingolimod administration was associated with a significant modulation of neuroinflammatory and protective genes (CD11b, Foxp3, iNOS, Il1β, Il10, Arg1, and Bdnf) in motor cortex and spinal cord of animals. Our data show, for the first time, that fingolimod is protective in ALS mice and that its beneficial effects are accompanied by a modulation of microglial activation and innate immunity. Considering that the treatment was started in already symptomatic mice, our data strongly support fingolimod as a potential new therapeutic approach to ALS.

Keywords: Amyotrophic lateral sclerosis (ALS); FTY720; Fingolimod; mSOD1G93A mice; neuroinflammation.

MeSH terms

  • Amyotrophic Lateral Sclerosis / complications
  • Amyotrophic Lateral Sclerosis / drug therapy*
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Animals
  • Body Weight / drug effects
  • Body Weight / genetics
  • Brain / metabolism
  • Brain / pathology
  • Cytokines / genetics
  • Cytokines / metabolism
  • 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
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Movement Disorders / drug therapy
  • Movement Disorders / etiology
  • Mutation / genetics
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics


  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Immunosuppressive Agents
  • Nitric Oxide Synthase Type II
  • SOD1 G93A protein
  • Superoxide Dismutase
  • Fingolimod Hydrochloride