L-carnitine suppresses the onset of neuromuscular degeneration and increases the life span of mice with familial amyotrophic lateral sclerosis

Brain Res. 2006 Jan 27;1070(1):206-14. doi: 10.1016/j.brainres.2005.11.052. Epub 2006 Jan 17.


Amyotrophic lateral sclerosis (ALS) is a fatal disease caused by progressive degeneration of motor neurons in the spinal cord and motor cortex. Although the etiology of ALS remains unknown, a mutation of the gene encoding Cu,Zn-superoxide dismutase (SOD1) has been reported in 20% of familial cases of ALS (FALS). Transgenic mice that overexpress a mutated human SOD1 exhibit a phenotype and pathology similar to those observed in patients with FALS. Mitochondrial abnormality has been reported in patients with ALS and in animal models of FALS. We recently reported that L-carnitine, an essential cofactor for the beta-oxidation of long-chain fatty acids, effectively inhibits various types of mitochondrial injury and apoptosis both in vitro and in vivo. The present study demonstrates that oral administration of L-carnitine prior to disease onset significantly delayed the onset of signs of disease (log-rank P=0.0008), delayed deterioration of motor activity, and extended life span (log-rank P=0.0001) in transgenic mice carrying a human SOD1 gene with a G93A mutation (Tg). More importantly, subcutaneous injection of L-carnitine increased the life span of Tg mice (46% increase in male, 60% increase in female) even when given after the appearance of signs of disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Amyotrophic Lateral Sclerosis / genetics
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology*
  • Animals
  • Apoptosis / drug effects
  • Carnitine / administration & dosage
  • Carnitine / pharmacokinetics
  • Carnitine / pharmacology*
  • Disease Progression
  • Female
  • Guanine
  • Hindlimb
  • Humans
  • Injections, Subcutaneous
  • Longevity / drug effects*
  • Male
  • Mice
  • Mice, Transgenic
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / physiopathology*
  • Mutation
  • Nerve Degeneration / prevention & control*
  • Nerve Tissue Proteins / metabolism
  • Oxidation-Reduction / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxide Dismutase-1
  • Vitamin B Complex / administration & dosage
  • Vitamin B Complex / pharmacokinetics
  • Vitamin B Complex / pharmacology*


  • Muscle Proteins
  • Nerve Tissue Proteins
  • SOD1 protein, human
  • Vitamin B Complex
  • Guanine
  • Sod1 protein, mouse
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • Adenine
  • Carnitine