Multiple System Atrophy (MSA) is a progressive neurodegenerative disorder due to the loss of various neuronal populations, including the GABAergic and the dopaminergic systems in the striatum and in the midbrain. The resulting degeneration of the nigro-striatal circuit is responsible for a severe neurological involvement characterized by parkinsonism and cerebellar phenotypes. The neuropathological hallmarks of MSA consist of alpha-synuclein aggregations in oligodendrocytes and neurons. No disease-modifying therapy is available for this disorder, resulting in a reduced life-span of affected patients with a median survival of 6-9 years. This is largely due to the lack of reliable human models capable of reproducing key features of the disease and that could be tested for drug-development applications. Here, we aim to generate advanced 3D models of MSA derived from patients by developing brain region-specific organoids with midbrain and striatum identities. However, their application to the study of MSA has yet to be explored. We generated long-term culture of midbrain and striatum organoids from one MSA subject and one healthy donor and have extensively characterized these cultures demonstrating their appropriate differentiation. Specifically, organoids showed a correct spatial and temporal progression in the expression of genes involved in the human development of both midbrain and striatum. These models display several cell populations, particularly enriched in neurons (GABAergic, dopaminergic, glutamatergic) and glia (astrocytes, oligodendrocytes). We are currently exploring the fusion of these two brain region-specific organoids into a nigro-striatal assembloid which may be able to recapitulate the fundamental pathology observed in MSA brains.