Drugs to fix "misfolded" proteins could cure a range of diseases
By Darren Quick
December 9, 2013
Proteins adopt their functional three-dimensional structure by the folding of a linear chain of amino acids. Gene mutation can cause this folding process to go awry, resulting in "misfolded" proteins that are inactive or, in worse cases, exhibit modified or toxic functionality. This is the cause of a wide range of diseases, but researchers have developed a technique that fixes these misfolded proteins, allowing them to perform their intended function, thereby providing a potential cure for a number of diseases.
Up until relatively recently, scientists believed that misfolded proteins that were inactive were intrinsically non-functional. However, it was discovered that their inactivity was due to the cell's quality control system misrouting them within the cell. Drugs called "pharmacoperones," which get their name from their ability to act as so-called "protein chaperones," have the ability to enter cells and fix the misfolded proteins so they can be routed correctly, thus restoring their functionality.
Although this process has been observed under a microscope in recent years, a team led by P. Michael Conn, Ph.D. while at Oregon Health & Science University (OHSU) has become the first to demonstrate it in a living laboratory animal. The team was able to cure mice of a disease that makes the males unable to father offspring. Because the identical disease also occurs in humans, Conn believes the same technique will work in people.
The team says neurodegenerative diseases, such as Alzheimer's, Parkinson's and Huntington's, as well as certain types of diabetes, inherited cataracts and cystic fibrosis are just a few of the diseases that could potentially be cured using the new approach.
Conn, who is now at the Texas Tech University Health Sciences Center (TTUHSC), and his team are now looking to conduct clinical trials to see if the new drug treatment does indeed work in humans.
The team, which included Jo Ann Janovick, Douglas Stocco, Ph.D. and Pulak Manna, Ph.D., from TTUHSC, Richard R. Behringer, Ph.D. from the University of Texas MD Anderson Cancer Center and M. David Stewart, Ph.D. from the University of Houston, will have their work published this week in the early online edition of the Proceedings of the National Academy of Sciences.