SMA is a neurodegenerative disease caused by loss of the gene survival motor neuron-1 (SMN-1). The disease is inherited by approximately one in 6,000 children and currently has no cure. While the SMN-1 gene is missing, all SMA patients carry a nearly identical copy gene, SMN-2. Although the SMN-2 coding sequence has the potential to produce full-length SMN, nearly 90% of SMN2-derived transcripts are alternatively spliced and encode a truncated, nonfunctional protein.
In the current study investigators at the University of Missouri (Columbia, USA) explored the possibility of using a novel class of bifunctional RNA molecules to induce SMN-2 to direct the synthesis of intact SMN molecules. Toward this end, suitable RNAs were injected directly into the brains of SMA mice.
Results published in the October 25, 2011, online edition of the journal Molecular Therapy revealed that bifunctional RNA injections were able to elicit robust induction of SMN protein in the brain and spinal column of neonatal SMA mice. The RNA treatment significantly extended lifespan and increased weight in these animals.
“When we introduced synthetic RNA into mice that carry the genes responsible for SMA, the disease's severity was significantly lowered,” said senior author Dr. Chris Lorson, professor of molecular microbiology and immunology at the University of Missouri. “The mice that received synthetic RNA gained more weight, lived longer, and had improvements in motor skills. These results are very exciting.”
“It has been remarkable to watch how quickly SMN-2 knowledge has transformed from basic molecular biology to being modified targets for novel therapeutics,” said Dr. Lorson. SMN-2 is like a light that has been dimmed, and we are trying anything to get it brighter. Even turning it up a little bit would help dramatically.”
While these early results are promising, Dr. Lorson cautioned that considerable additional research is needed before synthetic RNA could be used to treat humans for SMA.
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