Multi-omics approach to predict therapeutic targets for multiple system atrophy

• Applicants: Professor Dr. Günter Höglinger; Dr. Otto Windl, since 8/2019
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2019 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 418452464

Multiple system atrophy (MSA) is a devastating neurodegenerative disease, leading to death within 6-10 years. Symptoms of MSA affect the mobility and the autonomic nervous system. Available drugs only provide limited symptomatic relief. There is no cure for MSA available. MSA is caused by aggregation of alpha-synuclein protein in neurons and oligodendrocytes (support cells) in the brain. Deeper understanding of the molecular causes and consequences of alpha-synuclein aggregation, leading to neurodegeneration is highly important to develop better therapies.We have previously generated large datasets in patient-derived materials (genome-wide association study, epigenome-wide DNA methylation study) and corresponding cell models (DNA-methylome, miRnome, transcriptome, proteome, siRNA modifier screen, functional compound screen). In this project, we will generate a large-scale dataset on many biological levels (epigenome, transcriptome, proteome) of the two cell types affected in MSA (neurons, oligodendrocytes), derived from human post-mortem brains and induced pluripotent stem cells from MSA patients and controls.These unique datasets will be explored using state-of-the-art powerful computational methods to generate an integrated map of the molecular pathways involved in MSA.This project is only possible in an international collaboration bringing together experts in various scientific areas. We expect to generate a unique and large database, which will be shared with the scientific community to accelerate the development of novel breakthrough therapies for MSA.

• DFG Programme: Research Grants
• International Connection: France, Netherlands, Switzerland
• Cooperation Partners: Professor Marc Bickle, Ph.D.; Professorin Jeanine Houwing-Duistermaat, Ph.D.; Professor Hilal Lashuel, Ph.D.; Professor Jörg Tost, Ph.D.
• Ehemaliger Antragsteller: Professor Dr. Armin Giese, until 7/2019