203 Curing the Shaking Palsy: How to Find a Treatment for Parkinson’s Disease?

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【Prerequisites】

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The students should have a basic understanding of biochemistry and cell biology (e.g., how DNA is transcribed to RNA, which then gets translated to protein; what are lipids, and wherein the cell do we find lipids)

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【Description】

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The English physician-scientist James Parkinson described the “Shaking Palsy” in 1817. More than 200 years later, we understand the underlying biology of “Parkinson’s disease” (PD) to some extent, we know that a protein called “alpha-synuclein” aggregates in patients’ brains, we know genetic and environmental risk factors, and we can treat patients symptomatically. But why has it so far been impossible to develop a therapy that truly stops or even reverses pathology? What cellular pathways should we target with small molecule strategies? Are lipid pathways worth investigating? Beyond small molecules, what approaches might be promising: antibody therapies? Gene editing? Tissue replacement? And why has it likewise been impossible to find suitable biomarkers to diagnose and study the progression of PD? What could turn out to be a viable biomarker for PD? Lastly, what makes PD unique among neurodegenerative diseases, and what does it have in common with Alzheimer’s, Frontotemporal Dementia, and other brain diseases?

 

This research workshop will delve into exploring many such questions. In Module 1, Professor Dettmer will guide students in original research on the discovery of alpha-synuclein as the essential protein in PD pathogenesis and attempts that have been made towards harnessing this insight into therapeutics. In the course, students will deepen their understanding of brain anatomy and brain biology and the degeneration that occurs in PD, causing the hallmarks of PD: Lewy body formation, neuronal loss in specific brain areas, and motor phenotypes. Potential intervention strategies will be evaluated.  Biomarkers for diagnosis and drug development will be discussed, and possible biomarker strategies will be highlighted.

 

During Module 2, students will work with Professor Dettmer to develop a research topic that involves literature review and creative thinking. The goal is to outline novel strategies towards (early) diagnosis and treatment of PD, including the combination of different approaches.  The project will hinge on studying the literature on existing systems and incorporating ideas based on a deepened understanding of brain biology. The deliverable for the project will be a written report that includes drawings and images and a final presentation.

 

【Sample research topics】

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• Can we find drug targets for PD in lipid pathways? What types of lipids exist, and which ones play a role in Parkinson’s and why?

•  Is it realistic to leverage gene editing for the treatment of PD?

• Why is it essential to find a biomarker to develop a treatment for PD? What options exist to develop biomarkers, and which one may be most promising?

• What drugs against PD are currently being tested in humans? What could a combination therapy against PD look like?