Small molecules, which allow complete control over a genetic defect responsible for muscular dystrophy have been discovered by scientists.
These small molecules will enable scientists to investigate potential new therapies and to study the long-term impact of the disease.
The Scripps Research Institute (TSRI) Associate Professor Matthew Disney said that this easy approach is an entirely new way to turn a genetic defect off or on.
Myotonic dystrophy is an inherited disorder, the most common form of a group of conditions called muscular dystrophies that involve progressive muscle wasting and weakness.
Myotonic dystrophy type 1 is caused a type of RNA defect known as a "triplet repeat," a series of three nucleotides repeated more times than normal in an individual's genetic code.
In this case, a cytosine-uracil-guanine (CUG) triplet repeat binds to the protein MBNL1, rendering it inactive and resulting in RNA splicing abnormalities.
To find drug candidates that act against the defect, Disney and his colleagues analyzed the results of a National Institutes of Health (NIH)-sponsored screen of more than 300,000 small molecules that inhibit a critical RNA-protein complex in the disease.
The team divided the NIH hits into three "buckets"-the first group bound RNA, the second bound protein, and a third whose mechanism was unclear. The researchers then studied the compounds by looking at their effect on human muscle tissue both with and without the defect.
Startlingly, diseased muscle tissue treated with RNA-binding compounds caused signs of the disease to go away. In contrast, both healthy and diseased tissue treated with the protein-binding compounds showed the opposite effect-signs of the disease either appeared (in healthy tissue) or became worse.
The new compounds will serve as useful tools to study the disease on a molecular level.
The findings have been published by the journal Nature Communications.