omicSynth: an Open Multi-omic Community Resource for Identifying Druggable Targets across Neurodegenerative Diseases.

Treatments for neurodegenerative disorders remain rare, although recent FDA approvals, such as Lecanemab and Aducanumab for Alzheimer's Disease, highlight the importance of a mechanistic approach in creating disease modifying therapies. As a large portion of the global population is aging, there is an urgent need for therapeutics that can stop disease progression and eliminate symptoms. In this study, we create an open framework and resource for evidence based identification of therapeutic targets for neurodegenerative disease. We use Summary-data-based Mendelian Randomization to identify genetic targets for drug discovery and repurposing. In parallel, we provide mechanistic insights into disease processes and potential network-level consequences of gene-based therapeutics. We identified 116 Alzheimer's disease, 3 amyotrophic lateral sclerosis, 5 Lewy body dementia, 46 Parkinson's disease, and 9 Progressive supranuclear palsy target genes passing multiple test corrections (p SMR_multi < 2.95E-06 and p HEIDI > 0.01). We created a therapeutic scheme to classify our identified target genes into strata based on druggability and approved therapeutics - classifying 41 novel targets, 3 known targets, and 115 difficult targets. Our novel class of genes provides a springboard for new opportunities in drug discovery, development and repurposing in the pre-competitive space. We also provide a user-friendly web platform to help users explore potential therapeutic targets for neurodegenerative diseases, decreasing activation energy for the community [ https://nih-card-ndd-smr-home-syboky.streamlit.app/ ].