MedicalResearch.com: What is the background for this study?
Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets.
MedicalResearch.com: What are the main findings?
Response: Following 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.
MedicalResearch.com: What should readers take away from your report?
Response: Development of a PhysioMap can facilitate greater understanding of the biological uncertainties that impact drug response. Systematically organizing the available public and proprietary data into a coherent graphical representation of the disease pathophysiology and drug mechanism of action is an efficient way to identify key uncertainties, generate hypotheses, and focus experimental designs.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: In the case of the current project, the Rosa team recommended follow up experiments to measure macrophage phagocytosis function, identify synuclein sites of action, assess the effect of mitochondrial dysfunction on vesicle trafficking, and evaluate the role of SNARE in macrophage function.
MedicalResearch.com: Is there anything else you would like to add?
Response: Development of a PhysioMap provides a unique capability to better understand and communicate the key elements and uncertainties of biologic systems in healthy and disease, and can be used to generate and test hypotheses to efficiently advance drug development programs.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation: poster presentation at the4th World Parkinson Congress
Abstract: Development of a qualitative systems pharmacology model to support hypothesis generation and testing for Parkinson’s disease.
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