Rare Variants: Shared Paths for Therapeutic Development and Neurobiological Investigation

Excerpt

The revolution in human genetics has led to the identification of hundreds of rare genetic variants that underlie neuropsychiatric disorders. This technological leap presents both an opportunity and a dilemma for developing new therapies. Monogenic diseases are simpler to study and can be used to develop a road map for progressing from a genetic cause to both an understanding of neurobiology and a disease-modifying therapy. This trajectory involves the development of cellular and animal models, the understanding of the natural history of a disease, and the identification of biomarkers and clinical endpoints. However, the large number of mutations and the rarity of the diseases requires criteria for prioritization and strategies for connecting these diseases to more common causes of neuropsychiatric disorders. The goal of this chapter is to provide a road map to help prioritize investments that will improve our understanding of rare neuropsychiatric diseases, connect these diseases to common disorders, and help to catalyze the development of new therapies.