Alexis Zajicek 1, Brian Haner 1, Melville Osborne 1, Moriah Jacobson2, Michael Carr2, Taleen Hanania1
Affiliation Details:
1 Psychogenics Inc, Paramus NJ, USA
2 Taconic Biosciences, Inc., Rensselaer, NY
Amyotrophic lateral sclerosis (ALS) is a fatal neurological disorder characterized by progressive motor neuron degeneration resulting in muscle weakness, paralysis, and eventually death. Mutations of the superoxide dismutase 1 (SOD1) gene are linked to familial and sporadic cases of ALS. In collaboration with Taconic Biosciences, PsychoGenics characterized a SOD1 G93A overexpressing (NTac:SD-Tg(SOD1G93A)L26H) rat model of ALS.
Male and female wild type (WT) and transgenic (Tg) rats were used in the study. Fifteen rats were enrolled in each group which allowed us to assess phenotypic differences in male and female rats. Body weight (BW), motor function, and nerve conduction changes were measured longitudinally starting at 16 weeks of age.
SOD1 rats show progressive decrease in BW and hindlimb grip strength starting at 24 weeks of age, whereas decreased locomotor and rearing activities occurred at 29 weeks of age. Deficits in rotarod performance were also seen in the SOD1 rats starting at 22 weeks of age. In general, the behavioral deficits were more robust in male SOD1 rats compared to female rats. Survival analysis showed that female rats survived longer than male rats.
Assessment of compound muscle action potential (CMAP) found that starting at 24 weeks of age, onset latency, which corresponds to the time from initiation of nerve stimulus to response, was increased in SOD1 rats. Peak amplitude and neuromuscular conduction velocity were reduced in SOD1 rats compared to WT rats. Additional marker analysis are ongoing.
Together, these results suggest that this model can be used for screening novel therapeutics for ALS treatment.