Protein production is a carefully orchestrated process that guides each new string of amino acids to fold into a specific, ordered shape.
A very small proportion of proteins made in the body do not form an ordered shape, but are said to be “intrinsically disordered”.
Usually, these poorly folded proteins are tightly controlled and degraded by the cell’s protein recycling system.
But in protein folding disorders, intrinsically disordered proteins are produced faster than they can be degraded.
If they stay as monomers they are relatively benign, but a small proportion of these proteins will bind together to form a template, onto which other proteins bind to form oligomers.
These oligomers can be highly toxic and pathogenic.
Oligomers stick together to become fibrils, and the accumulation of misfolded fibrils can lead to plaques. These processes ultimately cause cell dysfunction and cell death.
Therapies that aim to disrupt or break up plaques often end up generating more oligomers, which makes things worse.
And designing drugs to target these proteins is difficult due to the multitude of possible protein shapes.
Common Conformational Morphology (or “CCM”) technology, provides a method of finding similar binding sites for each type of intrinsically disordered protein.
CCM allows for rational design of drugs that neutralize the production of pathogenic templates… ultimately leading to fewer oligomers, fewer fibrils, and the potential to halt further progression in these diseases.