Rasagiline is a novel selective irreversible
monoamine oxidase-B (
MAO-B) inhibitor recently introduced for the symptomatic treatment of
Parkinson disease. Like other propargylamines
rasagiline has also shown
neuroprotective effects independent of
MAO-B-inhibition in various in vitro and in vivo models. The present study was performed to test the potential of
rasagiline as a disease-modifying agent in
multiple system atrophy (MSA) using a transgenic mouse model previously described by our group. (PLP)-
alpha-synuclein transgenic mice featuring glial cytoplasmic inclusion pathology underwent
3-nitropropionic acid intoxication to model full-blown MSA-like neurodegeneration. Two doses of
rasagiline were used (0.8 and 2.5 mg/kg) for a treatment period of 4 weeks.
Rasagiline-treated animals were compared to placebo saline-treated mice by evaluation of motor behaviour and neuropathology. Motor behavioural tests including pole test, stride length test and general motor score evaluation showed improvements in motor deficits associated with 2.5 mg/kg
rasagiline therapy. Immunohistochemistry and histology showed significant reduction of 3-NP-induced neuronal loss in striatum, substantia nigra pars compacta, cerebellar cortex, pontine nuclei and inferior olives of MSA mice receiving 2.5 mg/kg
rasagiline. The results of the study indicate that
rasagiline confers neuroprotection in a transgenic mouse model of MSA and may therefore be considered a promising disease-modifying candidate for human MSA.