Pharmacoperones – A New Way to Rescue Cells
While it appears to be a new technology, it has been a research project for 13 years and is finally showing beneficial effects in mouse models of disease. The procedure that has taken so long to develop has actually reversed a serious reproductive deficit in male mice. The condition in mice is parallel to the condition in humans, and the method perfected on mouse cells will also translate to human cells. This will be a major advance with wide ranging applications, particularly for neurodegenerative diseases such as PARKINSON’S DISEASE, Huntington’s disease and Alzheimer’s, among others.
When proteins such as alpha synuclein enter cells, they need to form a three dimensional structure in order to properly perform their function within the cell. When they do not form the proper structure, they are considered mis-folded proteins, which ultimately cause the cells to die. What this research has shown is that there are small molecules, which serve as a sort of “quality control” system, and when they encounter the misfolded proteins, they are unable to re-direct them thus causing them to fail. Use of another small molecule, a pharmacoperone, as a chaperone can enter the cell and serve as a scaffold to help the misfolded protein fold into the proper shape and then return to function. What is unique is that now they have found drugs to monitor the “quality control” system that can re-direct the misfolded proteins and rescue the cells. This is a whole new approach that may soon be able to cure a range of diseases
The team of researchers from Oregon Health Sciences University consisted of JoAnn Janovick and Michael Conn both of whom have recently left Oregon to join Texas Tech University Health Sciences. They were assisted in their research on this project by Richard, Behringer, M.David Stewart, Douglas Stocco and Pulak Manna. The research paper will be published in an early online edition of the Proceedings of the National Academy of Sciences.
Having seen such exciting and positive results in the mouse model, Dr. Conn is anticipating that clinical trials with humans will not be far in the future. Similar research is being carried out in other institutions for the treatment of diabetes, inherited cataracts and cystic fibrosis. Look for more exciting news and developments to come from this research in the near future.
Review by Marcia McCall