Table 2.
Preclinical trials in MSA models.
| Intervention | Animal model | Results |
|---|---|---|
| Riluzole (anti-glutamatergic drug) | Sequential double-toxin, double-lesion rat model (Scherfler et al., 2005) | Reduction of motor disturbances, reduction of the striatal lesion volume in the riluzole treated group compared to controls |
| MPTP + 3-NP mouse model (Diguet et al., 2005) | Riluzole improved motor scores and decreased neurodegeneration of striatal neurons | |
| Minocycline (tetracycline derivative) | Double-toxin, double-lesion rat model of MSA (Stefanova et al., 2004) | No behavioral effects, no neuronal protection, reduced microglial and astroglial activation |
| PLP-α-Syn mouse model of MSA (Stefanova et al., 2007) | Significant reduction of neurodegeneration in the SNpc and striatum | |
| Rasagiline (irreversible MAO-B inhibitor) | PLP-α-Syn mouse model of MSA combined with 3-NP administration (Stefanova et al., 2008) | Behavioral effects, relative preservation of olivopontocerebellar and striatonigral pathways |
| Rifampicin (antibiotic) | MBP-α-Syn mouse model (Shults et al., 2005, Ubhi et al., 2008) | Reduction of α-Syn aggregation |
| Nocodazole (microtubule-depolymerizing agent) | CNP-α-Syn mouse model of MSA (Nakayama et al., 2009) | Identified β-III-tubulin as key factor in α-Syn-aggregation, administration of nocodazole inhibited the aggregation of soluble α-Syn fibrils, but did not dissolve already formed aggregates |
| Terazosin (α1-AR antagonist) | α1B-Adrenergic receptor overexpressing transgenic MSA mouse model (Papay et al., 2002, Zuscik et al., 2000) | Long-term treatment improved motor deficits and reduced α-Syn-aggregation |
| Myeloperoxidase inhibitor (MPO) | PLP-α-Syn mouse model of MSA combined with 3-NP administration (Stefanova et al., 2012) | Reduced motor impairment, reduction of intracellular α-Syn aggregates, suppression of microglial activation, reduced degeneration in the striatum, SNpc, Purkinje cells, pontine nuclei and inferior olivary complex |
| Fluoxetine (selective serotonin reuptake inhibitor) | MBP-α-Syn mouse model of MSA (Ubhi et al., 2012) | Amelioration of motor behavior, reduction of α-Syn aggregation, astrogliosis and demyelination, increased GDNF and BDNF levels, neuroprotection in the frontal cortex, hippocampus and basal ganglia |
| Fluoxetine | MBP-α-Syn mouse model of MSA (Valera et al., 2013) | Reduction of α-Syn aggregation in the basal ganglia, reduced astrogliosis in basal ganglia and hippocampus, modulation of proinflammatory and anti-inflammatory cytokines |
| Olanzapine | ||
| Amitriptyline | ||
| Mesenchymal stem cells | PLP-α-Syn mouse model of MSA (Stemberger et al., 2011a) | Relative preservation of SN TH-positive neurons, downregulation of the T-cell specific cytokines IL-2 and IL-17 |
| MPTP-3-NP double-toxin mouse model (Park et al., 2011) | Increased survival of dopaminergic neurons in the SN and striatum, anti-inflammatory and anti-gliotic effects |