Overview of Protein Misfolding and Instability
Certain human diseases result from mutations in specific genes that, in many cases, lead to the production of proteins with reduced stability. Proteins with these mutations may not achieve their correct three-dimensional shape and are generally referred to as misfolded proteins. Misfolded proteins are often recognized by cells as having defects and, as a result, are eliminated prior to reaching their intended location in the cell. The reduced or completely absent biological activity of these proteins leads to impaired cellular function and ultimately to disease.
Our novel approach to the treatment of human genetic diseases caused by protein misfolding and instability consists of using a new type of drug, which we refer to as a pharmacological chaperone, that selectively binds to the target protein, which increases the stability of the protein and helps it fold into the correct three-dimensional shape. This restores appropriate trafficking of the protein, thereby increasing protein activity, improving cellular function, and reducing stress on cells.
Lysosomal storage disorders, such as Fabry disease, Gaucher disease, and Pompe disease, are just a few examples of diseases in which a protein folding defect is the primary cause of the pathology.