Objective: Objective: In order to improve the understanding of the alpha-synuclein system and its role in Parkinson’s disease, Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking by creating a PhysioMap, memorialize and communicate the current state of knowledge within Elan in a Synuclein Model Qualification Method Document (MQM), and to recommend experiments to test hypotheses, resolve uncertainties, and identify and prioritize potential targets.

Background: Background: Elan was developing inhibitors of alpha-synuclein formation for the treatment of Parkinson’s disease and wanted to improve the design and interpretation of in vitro assays to evaluate candidate compounds. 

Methods: Methods: The PhysioMap was developed using both publically available literature and proprietary Elan data. The Synuclein PhysioMap was designed and curated by a multidisciplinary team to represent synuclein synthesis and distribution within a neuron, SNARE complex formation, phagocytosis, cytokine release, neurotrophic factor release, and mitochondrial function.

Results: Results: During the development of the PhysioMap, the team identified key biological uncertainties and hypotheses and recommended focused laboratory experiments to gain a better understanding of synuclein function in Parkinson’s disease.

Conclusions: Conclusion: Development of the PhysioMap helped provide insight into the alpha-synuclein system and its function in Parkinson’s disease, and helped identify a more efficient experimental path for evaluating therapeutic compounds.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/application-of-a-qualitative-model-to-elucidate-the-role-of-the-alpha-synuclein-system-in-parkinsons-disease/