Multiple system atrophy (MSA) is an adult-onset, progressive neurodegenerative disorder which is clinically characterized by various combinations of cerebellar ataxia, Parkinsonism, autonomic dysfunction and pyramidal signs. MSA is known as a sporadic disease, however, multiplex families with MSA suggest a genetic predisposition to MSA. The advanced genome research will clarify the pathogenetic mechanisms of MSA, and the disease-modifying therapy of MSA may be available in the future. To clarify the natural history of MSA for the future therapeutic trials, and to elucidate the molecular pathogenetic mechanisms of MSA, JAMSAC (Japan MSA research consortium), a nationwide consortium, was established in 2003. In the view of the future therapeutic trial for MSA, it is essential to design appropriate end point, sample size, duration of the trial. And inclusion criteria are also important for effective therapeutic trial. We conducted a cross-sectional study on 225 MSA patients using unified multiple system atrophy rating scale (UMSARS). As inclusion criteria, we employed additional criteria based on specific MRI findings to recruit earlier stage patients. Sample size estimation from the longitudinal study suggested we need sensitive outcome measures beside UMSARS. JAMSAC is planning to a longitudinal study for natural history of MSA in Japan.