The analogy is often made comparing proteins with machines. It's an apt analogy, and like a bent or twisted machine, a misshapen protein is unable to function properly. Proteins are long chains of amino acids, folded into a certain configuration that allows them to perform a mechanical function. When they're folded incorrectly, they perform that function poorly or not at all, and that malfunction can lead to disease.
In humans, for example, misfolded proteins lay at the heart of diseases such as phenylketonuria (PKU) and cystic fibrosis. Many of these diseases have genetic origins, and much research has focused on correcting the gene. An alternative approach may be to look for an agent that can restore a protein to its proper shape. This approach might, in theory, also restore the protein's function.
Indeed, in nature, molecules called "chaperones" facilitate correct protein folding. Angel Pey and colleagues at the University of Bergen in Norway, the Universidad de Zaragoza in Spain, the Biocomputation and Complex Systems Physics Institute also in Zaragoza, and the University of Zurich in Switzerland, tested a panel of chemicals to see whether any would act like chaperones and restore the shape and function of the protein phenylalanine hydroxylase (PAH), the protein when misfolded leads to PKU.In a report in the Journal of Clinical Investigation, the team reports that several chemicals showed evidence of improving activity in animal models. It remains to be seen whether these particular compounds can be developed into drugs. But the larger message for drug developers is that it may be worthwhile to look for drugs with chaperone-like activity when trying to reverse the symptoms of genetically determined diseases.
Source: A.L. Pey et al., "Identification of Pharmacological Chaperones as Potential Therapeutic Agents to Treat Phenylketonuria," Jrnl. of Clin. Invest. 118, 2858–2867 (2008).