Scripps team develops new platform tech for RNA-defect diseases


Investigators at the Scripps Research Institute in Florida have developed a platform technology that they believe could have an impact treating a range of rare diseases triggered by a common defect in RNA.

The team, led by Matthew Disney, focused on an RNA structure that triggers spinocerebellar ataxia type 10 (SCA10), a form of spinocerebellar ataxia. 

SCA10, they note, is caused by a pentanucleotide repeat--a genetic sequence of five nucleotides repeated “many more times than normal”--which affects the mitochondria, the cell's energy-producing plant. They developed a new drug, dubbed 2AU-2, that binds to the RNA base pairs. And they tested it on cells taken from patients, the first preclinical evidence that they may be on the right track.

"More than 30 diseases, all of them incurable, are caused by RNA repeats," said Disney, citing Huntington's disease, fragile X-associated tremor ataxia syndrome and myotonic dystrophy type 1 and 2. "By a thorough basic science investigation, we identified small molecules that target RNA base pairs precisely. We then leveraged this information to design the first drug candidate that binds to disease-causing defects in SCA10. Application of the drug candidate returns certain aspects of those cells to healthy levels--it's like the defect is not even there."

The team has also been developing new tools that can be used to assess the way drug candidates interact with the base pairs, working up several potential candidates for possible clinical work.

"The potent bioactivity of 2AU-2 to moderate the structurally induced toxicity in SCA10 strongly suggests that base-pair-targeting RNA modules could have broad applicability in our effort to develop other compounds that target different RNAs," said TSRI Research Associate Wang-Yong Yang, the first author of the study. "More than 70 percent of RNA secondary structure is made up of base pairing."

- here's the release