Targeted Therapeutics for Rare Disorders

Rare diseases affect almost 6% of the world's population and are responsible for significant loss of health, life and economic potential. The vast majority of rare diseases are due to genetic variants that result in the loss or alteration of a protein that is needed for cells and organs to function normally. Few rare diseases have an approved treatment, making individuals with rare diseases collectively one of the most underserved communities in medicine today. The few treatments that have been available typically have focused on disease symptoms, without correcting or addressing the cause of disease, the underlying mutation. Hence, there is a drive to develop therapeutics that repair, replace, or alter DNA, RNA, or proteins responsible for rare disease. Herein, we focus on mutation targeted approaches including gene editing, gene replacement, RNA editing, and gene/protein regulation modalities including antisense oligonucleotides, nonsense suppression therapeutics, and protein modulators. We discuss how each approach works, what types of variants might be targeted, advantages, disadvantages, and successes. We also highlight other concerns such as delivery methods and the need to consider patient perspectives. Advocacy groups have been instrumental in rare disease therapeutics.