Researchers Find 2 New Ways to Tackle RNA Diseases Such as MD

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by Alice Melão |

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MD gene variations and apabetalone

Scientists have developed two new approaches to kill RNA molecules responsible for incurable diseases such as muscular dystrophy (MD),  according to a study.

One is designing small molecules that destroy only disease-causing RNA. The other approach is using a disease-causing RNA as a catalyst to create a therapy that kills the RNA.

A team from The Scripps Research Institute (TSRI), led by Professor Matthew Disney and Research Associate Suzanne Rzuczek, conducted the study, “Precise small-molecule recognition of a toxic CUG RNA repeat expansion.” It was published in the journal Nature Chemical Biology.

The researchers focused on RNA that causes a version of MD known as myotonic dystrophy type 1, but said their approach could be used to combat other RSA diseases.

RNA molecules are responsible for several essential cell mechanisms. Sometimes they lapse into uncontrolled activity that researchers believe triggers disease.

Scientists have struggled to find ways to tackle over-active RNA. Treatments they have developed so far have either proved ineffective or ailed to target only aberrant RNA molecules.

“We present for the first time multiple solutions to this long-standing problem,” Disney said in a press release. “With the precision of a surgeon’s scalpel, we have shown that small molecules can be designed to seek out and destroy only disease-causing RNA. Further, we developed novel chemical approaches to use a disease-causing RNA to help make its own drug by using that RNA as a catalyst for drug synthesis at the needed site. It is like having your physician place a drug at the right place without exposing healthy cells.”

A defect known as triplet repeat — repetition of a sequence more times than normal in the genetic code — can cause diseases by creating a larger-than-usual RNA molecule with abnormal activity.

The researchers designed molecules that could target these larger, disease-associated RNA rather than shorter, normal RNA.

They also found a new way to use imaging to track RNA molecules.

“We have brought RNAs out of the darkness and into the light by developing a chemical flare that goes off when a drug targets the RNA in a diseased cell and then continues to track the RNA’s movement,” Disney said.

Professor Ryohei Yasuda of the Max Planck Florida Institute for Neuroscience, a co-author of the study, said his team observed “a huge difference in signal” between “disease cells and normal cells under our microscope technique.”

“The combination of cutting-edge chemistry and microscopy techniques developed in Florida is a powerful approach to identify new methods to probe and manipulate (and kill) disease-causing RNA in cells,” Lesley Colgan, another study co-author, said.