5.1 Background The disease: MSA is a synucleinopathy that is suitable for various reasons as a model disease to investigate disease-modifying effects in α-synuclein (aSyn)-dependent neurodegeneration. The disease progression is more rapid compared to PD and therefore allows the observation of clinically relevant effects in shorter observation periods. As no potent symptomatic treatment of MSA is currently available, the influence of symptomatic active substances on clinical data is limited and placebo can be used as comparator. This solves the potential ethical problem of having to deprive patients of such symptomatic treatment during the study and underlines the high medical need for a symptomatic treatment. Another important argument for neuroprotection studies in MSA is that in three independent studies EMSA, NNIPPS, MEMSA a very similar disease progression was observed over a defined period of time, which enables a precise power analysis with sample sizes and follow-up periods that are suitable for an investigator initiated trial (IIT).