Abstract
Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive degeneration of motor neurons leading to muscle atrophy, paralysis and eventual death of the patients within 2-5 years from onset of symptoms. To date, there is no cure for ALS.
Mutations in superoxide dismutase 1 (SOD1) gene, encoding an antioxidant enzyme, were the first discovered genetic cause for ALS2. A mouse model carrying mutations in the SOD1 gene shows ALS-like clinical symptoms and progressive degeneration of motor neurons.This study had two aims: i) Characterize the phenotype of our SOD1-G93A mouse model of ALS and, ii) study the effects of a novel molecule in this animal model.
Methods
Female and male SOD1-G93A mice (B6SJL-TgN (SOD1-G93A)1Gur, Jackson Laboratory) and wild-type littermate controls were used in the present study. The phenotype of the mice was studied by monitoring body weight, progression of the symptoms, muscular strength and motor coordination.
To study the effects of a novel molecule we used Alzet minipumps to deliver continuous infusion of the compound into the lateral ventricle of the brain for 28 days. To evaluate the effect of the drug we monitored the same parameters as in the characterization of the animal model. Paralyzation of the hind limbs was used as the endpoint of study after which mice were sacrificed and samples from lumbar spinal cord, gastrocnemius muscle and brain were collected for post-mortem analysis.
Results
The phenotype of our SOD1-G93A mouse model was comparable to the others reported earlier.
The novel molecule studied here significantly improved motor coordination and maintained body weight at the late stage of the disease. Furthermore, it increased the survival of the SOD1 mice by approximately 6 days.
Conclusions
The SOD1-G93A mouse model mimics ALS-like clinical symptoms and it is a useful tool for in vivo drug testing.
Although the molecular mechanisms and signaling pathways underlying the effects of our novel molecule remain to be clarified, this compound holds a great promise for the treatment of ALS.
