Targeting USP14, a protein that suppresses proteostasis

In December 2020, Proteostasis and Yumanity had a reverse merger, with the management of Yumanity taking over and the merged company taking the name Yumanity. It is unclear if Proteostasis’s programs are continuing, as they do not appear on the website and correspondence with the company failed to provide an answer.

Proteostasis Therapeutics was developing drugs that inhibit USP14, a protein that suppresses proteasomes, which are responsible for degrading unwanted proteins within cells. Its research suggests that this will reduce proteasomic function and so reduce the amount of dangerous aggregates within the human brain, such as the tau protein associated with Alzheimer’s disease and the α-synuclein associated with Parkinson’s.

Working under a proteostasis network model, which measures and defines proteostasis by the amounts and relationships of more than a thousand proteins, Proteostasis Therapeutics was using an -omics-based approach to develop therapeutic compounds that can restore balance to this network.

The company also planned to have a drug in a Phase 1 clinical trial that modulates the cystic fibrosis transmembrane conductance (CFTR) protein as a method of treating cystic fibrosis.