Matthew Disney, associate professor of chemistry at The Scripps Research Institute in Jupiter, Fla., was awarded an MDA research grant totaling $362,724 over a period of three years to test the ability of compounds he has developed to target the toxic RNA in myotonic dystrophy type 2 (MMD2, also known as DM2).
MMD2 is caused by an abnormally expanded section of DNA on chromosome 3, which leads cells to make an abnormally long segment of RNA from it. This expanded RNA folds into a structure that traps certain cell proteins, preventing them from doing their normal jobs.
Disney’s research group has designed small molecules that bind specifically to this expanded RNA. If these, or molecules like them, can reduce the amount of protein the RNA can trap, they may be useful as therapy for MMD2. Disney will be testing these molecules for that ability, and also determining the three-dimensional structure of the MMD2 RNA.
“If we are successful in these endeavors we will be able to better understand how DM2 RNA binds to and inactivates proteins,” he says. That should provide the foundation for development of better and more specific molecules that can be tested as drugs in people with MMD2.
“This is very much a developing field, and a lot of work is needed to establish if small molecules can be designed to target RNA and have therapeutic utility,” Disney says. “These studies are critically important because biologists are doing such a phenomenal job in identifying the biochemical mechanisms of disease. The major question is whether we can leverage this mechanistic information into small-molecule therapies.”
Funding for this MDA grant began Feb. 1, 2013.