Proteostasis Therapeutics, Inc. is pursuing a novel approach to therapeutic intervention based upon an understanding of the Proteostasis Network. Advances in our ability to characterize and pharmacologically control the Proteostasis Network create new opportunities for ameliorating diseases in a number of therapeutic areas.
The maintenance of protein homeostasis is essential to human health. When working properly, the Proteostasis Network (PN) ensures that every protein within a cell will reach its final destination correctly folded with appropriate function or be degraded and cleared to prevent damage. Disease, genetic mutations, environmental factors, and aging can cause the PN to become imbalanced, which can lead to a decrease in protein quality control contributing to diseases categorized as loss-of-function or gain-of-toxic function disorders. Loss-of-function diseases, such as cystic fibrosis, are often caused by inherited mutations resulting in inefficient folding and excessive degradation. Gain-of-toxic-function disorders, which include Alzheimer’s, Huntington’s, and Parkinson’s diseases, arise from protein aggregation-associated toxicity that overwhelms the rate of protein clearance inside or outside of the cell.
Proteostasis Therapeutics is developing novel therapeutics designed to pharmacologically control the PN, either by restoring its normal state or enhancing the capacity of the compromised PN to create a therapeutic state sufficient to control or delay progression of disease. This novel approach of rebalancing the PN offers a broader application to genetic diseases than protein replacement therapy by providing access to many cell types, organelles, and tissues where recombinant proteins cannot be delivered. Further it allows for improvement relative to single chaperones with the potential to address multiple diseases using the same therapeutic intervention. Our drug candidates should also complement existing strategies, with improved folding synergizing with molecular chaperones and intracellular clearance enhancing extracellular protein clearance approaches.