Researchers at the University of Texas (UT) Southwestern Medical Center identified synthetic RNA and DNA that can reverse the protein deficiency that causes Friedreich’s ataxia (FA), a neurological disease with no known cure. Their study, “Activating frataxin expression by repeat-targeted nucleic acids,” was published in the journal Nature Communications.
FA results from modifications to certain DNA sequences that inhibit cells from producing enough frataxin. The lack of this needed protein can lead to a number of complications, such as loss of muscular control, fatigue, hearing or vision impairment, slurred speech, and severe heart conditions. With the use of synthetic RNA or DNA introduced into patient-derived cells, the researchers identified a way to allow normal frataxin production to resume.
“The problem arises because of a mutation within the frataxin gene FXN that does not code for protein. In this case, the mutation causes the synthesis of a longer piece of RNA. This longer sequence binds the DNA and gums up the works, blocking RNA production needed to produce the frataxin protein,” Dr. David Corey, professor of Pharmacology and Biochemistry at UT Southwestern and the study’s senior author, said in a press release.
“The synthetic DNA or RNA prevents the mutant sequence from bending back and blocking the frataxin gene. This action activates the frataxin gene, which then makes frataxin RNA and protein at normal levels,” Dr. Corey said. “In addition, our approach is selective for targeting the frataxin gene FXN and does not affect other genes.”
Unlike CRISPR (clustered regularly-interspaced short palindromic repeats) genomic editing technique, which relies on gene modification, this study’s molecules are synthetic. This RNA and DNA also belong to classes of molecules already in clinical use, so the development of a new therapy based on their use should be fairly straightforward, he said.
A subsequent challenge is adequately delivering the synthetic molecules to tissues affected by FA, Dr. Corey added, noting that such challenges are being addressed in ongoing clinical programs targeting other conditions, such as Huntington’s disease and spinal muscular atrophy (SMA).
According to the National Institute of Neurological Disorders and Stroke (NINDS), about one in 50,000 people are affected by FA, a disease whose onset typically begins between the ages of 5 and 18.