Muscular dystrophy affects Americans of all ages, though likelihood of survival decreases with age of onset. Muscular dystrophy is a group of disorders in which skeletal muscles weaken as a result of the deterioration of certain necessary proteins. As a genetic disorder that causes serious disability in a short period of time, the disease is currently incurable.

In a new study, researchers have used muscular dystrophy's genetic basis against the disease's malicious effects on the body. Alteration of the genes that cause dystrophy can actually turn the disease "off".

How does a disease turn off? A topical understanding of genetics is necessary to explain the process.

DNA is the body's genetic information. It decides which proteins and molecules will exist in that body. RNA, which is made from DNA, dictates the proteins and molecules made at a particular time. Proteins — if the RNA is made correctly from DNA — tend to carry out processes within the body, like digestion, or in the case of muscular dystrophy, muscle maintenance and other vital functions. This is the central dogma of biology. Genetic diseases arise when this dogma is disturbed.

In muscular dystrophy, the RNA is made improperly. A certain portion of it is coded incorrectly from DNA, causing ineffective proteins to be made. This is the crux of muscular dystrophy. The improperly made portion binds to a protein necessary for muscle maintenance and causes the wide array of symptoms related to muscular dystrophy. These symptoms include poor balance, drooping eyelids, respiratory difficulty, muscle spasms, and the eventual inability to walk.

It is important to note that the RNA and protein complex is essentially what causes the disease. When a person does not have muscular dystrophy, this complex does not occur. There are currently no drugs that can undo this association that creates muscular dystrophy. The only treatments that exist for the disease are therapies that attempt to strengthen muscles and encourage their use.

Scientists at The Scripps Research Institute in Florida have recently tested 300,000 drugs that may potentially ameliorate the RNA and protein complex from binding in the first place. They found that the drugs that could bind the RNA, instead of DNA or protein molecules, showed the most disease improvement. This indicates that the disease comes from the original protein binding to the RNA and causing conformational changes in protein made from that RNA thereafter.

"Now that we can reverse the disease at will, we can study those aspects of it," said Matthew Disney, Ph.D., associate professor of chemistry at Scripps. "This easy approach is an entirely new way to turn a genetic defect off or on."

And with this ability to turn a disorder on or off, more can be done to treat those suffering from it, thanks to molecular-level interventions of this genetic disorder.

 

Source: Childs-Disney JL, Stepniak-Konieczna E, Ilyas TT, et al. Induction and reversal of myotonic dystrophy type 1 pre-mRNA splicing defects by small molecules. Nature Communications. 2013.