Milestones in Medical Science

Scripps Research scientists create RNA repair technology

Matthew Disney, Associate Professor at Scripps Florida

Matthew Disney, Associate Professor at Scripps Florida

Researchers from the Florida campus of Scripps Research have identified a compound that can help repair a defect in RNA that is associated with a variety of incurable neurological and neuromuscular disorders.

In a new study, Matthew Disney, associate professor at Scripps Florida, describes a method to find compounds that target defective RNAs, specifically RNA that carries a structural motif known as an "expanded triplet repeat." That motif, a series of three nucleotides repeated many more times than normal in the genetic code of affected individuals, has been associated with diseases such as Huntington's disease, Spinocerebellar ataxia, and Kennedy disease.

"For a long time it was thought that only the protein translated from this type of RNA was toxic," Dr. Disney said. "But it has been shown recently that both the protein and the RNA are toxic. Our discovery of a small molecule that binds to RNA and shuts off its toxicity not only further demonstrates that the RNA is toxic, but also opens up new avenues for therapeutic development because we have clearly demonstrated that small molecules can reverse this type of defect."

In new research, Dr. Disney's team used a query molecule as a template to find similar but more active compounds to inhibit a toxic triplet repeat. One of these compounds was then found effective in inhibiting the RNA toxicity of the repeat in cells derived from patients, which demonstrated an improvement in early-stage abnormalities.

"The toxic RNA defect actually sucks up other proteins that play critical roles in RNA processing, and that is what contributes to these various diseases," Dr. Disney said. "Our new compound targets the toxic RNA and inhibits protein binding, shutting off the toxicity. Since the development of drugs that target RNA is extremely challenging, these studies can open up new avenues to exploit RNA drug targets that cause a host of other RNA-mediated diseases."

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