Congruence Therapeutics: finding a fix for misfolded proteins

All the instructions for proper folding are directly encoded in a protein’s amino acid sequence. This means that even subtle mutations affecting a single residue can derail the folding process, distorting that protein’s structure and thereby impeding or even fully disabling its function. Clarissa Desjardins, a serial biotech entrepreneur with a longstanding interest in developing therapies for rare diseases, recognized this vulnerability as an opportunity. “A lot of the rare diseases that I was looking at were partial loss of function due to misfolded proteins,” she says. “And I learned that these misfolded proteins can be stabilized by small molecules.” In 2021, Desjardins founded Congruence Therapeutics in Montreal with the goal of discovering and developing ‘pharmacological chaperone’ drugs that can effectively restore normal folding to mutated proteins.

doi: https://doi.org/10.1038/d41587-023-00009-5