Therapeutics for Huntington's Disease

Huntington’s disease is a devastating neurodegenerative disease with no current therapeutic options. The proposed work will identify novel therapeutic leads for development as badly needed new drugs in phase II studies. This will be achieved using a novel natural products-based approach.Natural products or their derivatives have accounted for most of our current drugs, demonstrating their unique status as “privileged” molecules that are well adapted for therapeutic use. However, natural products have previously been unsuitable for modern, high-throughput (HT) drug discovery screening approaches, and as such, were long ago abandoned in drug discovery programs of large pharma. The substitute has been high- throughput screening of combinatorial chemical libraries. These unnatural chemical libraries have yielded few new pharmaceutics leading to a significant decline in pharmaceutical drug discovery productivity.Recent research in the field of synthetic biology has identified numerous biosynthetic pathways, largely from microbial sources, that have the capacity to produce tremendous numbers of novel natural products that are suitable for high-throughput screening. In this work, Synthetic Biodesign will combine a novel biosynthetic approach with a novel whole-animal high-throughput screen to demonstrate that natural products can be reintegrated into the drug discovery pipeline and this can be done using modern HT methodologies.Natural products and their derivatives have been the greatest source of our current pharmaceutics. However, most pharmaceutical companies have moved away from the use of natural products in their drug discovery programs, to devastating effect. This was necessary due to the adoption of high-throughput screening approaches for which natural products were not readily adaptable. Synthetic Biodesign has developed a novel natural product-based drug discovery platform that is compatible with modern high-throughput screening methods. In the proposed work, Synthetic Biodesign will use this platform to provide badly needed new pharmaceutics for the treatment of important human diseases. In particular, novel therapeutics for the treatment of Huntington’s disease will be developed.