Table 1.

List of drugs and treatments tested in pre-clinical and clinical trials

Drug/Treatment	Pre-clinical studies	Clinical trial
Minocycline	Toxin MSA model (Stefanova et al. 2004b) anti-inflammatory, no neuroprotection Transgenic MSA model (Stefanova et al. 2007) anti-inflammatory, neuroprotection by early application	MEMSA-trial (Dodel et al. 2010) anti-inflammatory, no change in progression
Riluzole	Toxin model (Diguet et al. 2005; Scherfler et al. 2005) partial striatal neuroprotection, no motor improvement	NNIPPS study (Bensimon et al. 2009) no neuroprotection
Rifampicin	Transgenic MSA model (Ubhi et al. 2008) protective	RDCRC (clinicaltrials.gov NCT01287221) no neuroprotection
Rasagiline	Transgenic MSA model (Stefanova et al. 2008) protective	Multi-center study (Poewe et al. 2012) no change in progression
Fluoxetine	Transgenic MSA model (Ubhi et al. 2012) protective	French clinical trial (clinicaltrial.gov NCT01146548) negative outcome
MSCs	Toxin MSA model (Park et al. 2011) Transgenic MSA model (Stemberger et al. 2011) protective, immunomodulatory	South Korean clinical trial (Lee et al. 2008, 2012) delayed progression

Summary of putative neuroprotective and neuroimmunomodulatory treatments that were tested in pre-clinical studies. Due to the positive outcome in pre-clinical studies, clinical trials were conducted with the listed promising target drugs, yet the positive results gained in animal studies could not be replicated in MSA patients. Only the Korean study using mesenchymal stem cells (MSCs) could replicate the positive outcome of the pre-clinical trials. MEMSA-trial, Minocycline European Multiple System Atrophy-trial; NNIPPS, Neuroprotection and Natural History in Parkinson Plus Syndromes; RDCRC, Rare Diseases Clinical Research Consortia