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Drug Discovery

PAQ launches with $30 million to hijack autophagy for protein degradation

The startup will develop small molecules that label proteins, and other substances, for destruction in autophagosomes

by Ryan Cross
July 22, 2021 | A version of this story appeared in Volume 99, Issue 27


PAQ Therapeutics has launched with $30 million in series A financing. The Cambridge, Massachusetts–based start-up aims to design drugs that manipulate autophagy, a complex process sometimes described as cellular housecleaning. The goal is to remove unwanted proteins or other debris that accumulate inside cells.

It’s a fresh approach to the increasingly popular field of targeted protein degradation.

Most drug companies working in protein degradation are designing small molecules that hijack the ubiquitin-proteasome pathway in cells. These molecules grab hold of a target protein and connect it to an enzyme that tags the protein with ubiquitin molecules. That ubiquitin mark destines the target protein for degradation in a cell’s protein trash compactor, called the proteasome.

PAQ, in contrast, is hijacking autophagy, used to remove many unwanted things from cells, including lipids, protein aggregates, old organelles, and even pathogens. When autophagy is activated, these things are swept into vesicles called autophagosomes and broken down.

PAQ is developing small molecules it calls autophagosome-tethering compounds (ATTECs) that tag target proteins, or other substances, and send them to the autophagosome. The start-up isn’t disclosing specifics on how ATTECs work but proteins, lipids, organelles, and more are on the table as possible targets.

Some neuroscientists are excited about the possibility of boosting autophagy to destroy protein aggregates that accumulate in the brains of people with neurodegenerative diseases, such as amyloid β in Alzheimer’s disease and synuclein in Parkinson’s disease. PAQ’s first program will focus on an undisclosed genetic neurodegenerative disease.



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