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Pridopidine modifies disease phenotype in a SOD1 mouse model of amyotrophic lateral sclerosis
Author(s) -
EstévezSilva Héctor M.,
Mediavilla Tomás,
Giacobbo Bruno Lima,
Liu Xijia,
Sultan Fahad R.,
Marcellino Daniel J.
Publication year - 2022
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.15608
Subject(s) - amyotrophic lateral sclerosis , sod1 , phenotype , neuroscience , disease , medicine , psychology , biology , pathology , genetics , gene
Amyotrophic lateral sclerosis (ALS) is a lethal and incurable neurodegenerative disease due to the loss of upper and lower motor neurons, which leads to muscle weakness, atrophy, and paralysis. Sigma‐1 receptor ( σ ‐1R) is a ligand‐operated protein that exhibits pro‐survival and anti‐apoptotic properties. In addition, mutations in its codifying gene are linked to development of juvenile ALS pointing to an important role in ALS. Here, we investigated the disease‐modifying effects of pridopidine, a σ ‐1R agonist, using a delayed onset SOD1 G93A mouse model of ALS. Mice were administered a continuous release of pridopidine (3.0 mg/kg/day) for 4 weeks starting before the appearance of any sign of muscle weakness. Mice were monitored weekly and several behavioural tests were used to evaluate muscle strength, motor coordination and gait patterns. Pridopidine‐treated SOD1 G93A mice showed genotype‐specific effects with the prevention of cachexia. In addition, these effects exhibited significant improvement of motor behaviour 5 weeks after treatment ended. However, the survival of the animals was not extended. In summary, these results show that pridopidine can modify the disease phenotype of ALS‐associated cachexia and motor deficits in a SOD1 G93A mouse model.