Researchers Turn Off and On Defect related to Muscular Dystrophy in Cells
Myotonic dystrophy is an inherited disease that most commonly results in muscular dystrophy, which is a condition characterized by the progressive weakening and wasting of muscles in the body. Using knowledge of how myotonic dystrophy type 1 occurs, the researchers from the Scripps Research Institute (TSRI) on Florida campus were able to switch on and off the defect related to this condition in cells. This type of research could pave way for other scientists to develop preventative measures for genetic diseases.
"This is the first example I know of at all where someone can literally turn on and off a disease," said TSRI Associate Professor Matthew Disney, according to Medical Xpress. "This easy approach is an entirely new way to turn a genetic defect off or on."
The researchers knew that myotonic dystrophy type 1 results from a RNA defect known as triplet repeat. Triplet repeat occurs when a series of three nucleotides in RNA repeat more often than normal. In this case, the series responsible for the condition is the cytosine-uracil-guanine (CUG) triplet. CUG makes the protein, MBNL1 inactive, which then leads to RNA splicing abnormalities. For this study, the researchers used data from the National Institutes of Health's (NIH) sponsored screen of over 300,000 small molecules that appear to affect the RNA-protein complex that has been tied to the genetic disorder.
The researchers grouped the results into three different categories so that they can test the effects each group had on healthy and non-healthy human tissue. The first group was bound to RNA. The second group was bound to protein. The last group had unclear mechanisms. When the researchers used the first group to treat diseased muscle tissue, the group appeared to turn off the defect. However, when the researchers used group two on healthy and non-healthy muscle tissue, the defect seemed to worsen and had more symptoms.
"In complex diseases, there are always unanticipated mechanisms," Disney said. "Now that we can reverse the disease at will, we can study those aspects of it."
The study was published in the journal Nature Communications.