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CSHL Shows Correcting RNA Splicing May Help Treat Spinal Muscular Atrophy

PLoS Biology publishes "Enhancement of SMN2 Exon 7 Inclusion by Antisense Oligonucleotides Targeting the Exon"

Cold Spring Harbor, New York --  RNA splicing antisense technology studied at Cold Spring Harbor Laboratory (CSHL) effectively corrected an mRNA splicing defect found in spinal muscular atrophy (SMA) patients, and is now ready to be tested in mouse models.  “SMA patients who suffer from motor-neuron degeneration may benefit from our ability to correct the mRNA splicing defect that makes their SMN2 genes only partially functional,” suggested CSHL Professor Adrian Krainer, Ph.D.

RNA splicing antisense technology allows researchers to influence the ultimate structure and function of proteins. Proteins are synthesized from instructions coded in the DNA through a multi-step process that includes RNA splicing.  Information stored in the DNA of genes is transcribed into immature “pre-messenger RNAs” (pre-mRNAs), pre-mRNAs are then spliced into mature “messenger RNAs” (mRNAs), and finally, mRNAs are translated into proteins.  In humans and most other organisms, the splicing process thus ensures proper protein production.

“Targeting the splicing process is a promising strategy for finding new medicines to treat SMA, and possibly other diseases,” said Marcus Rhoades, Ph.D. of the National Institute of General Medical Sciences, which partially supported Krainer’s research.  “This work brings us one step closer to that goal.”

The defect in SMN2 gene expression in SMA patients is at the level of pre-mRNA splicing, such that exon 7 tends to be left out of the mRNA that ultimately makes SMN protein.  Several strategies have been pursued to increase the extent of exon 7 inclusion in the splicing of SMN2, for eventual use as therapeutics for SMA.  The Krainer team, in collaboration with a team at Isis Pharmaceuticals, surveyed a large number of antisense oligonucleotides (ASOs) and found that some of these ASOs are able to correct the mRNA splicing defect in cultured cells from SMA patients.  These powerful ASOs are identified by the Krainer team as viable for testing in mouse models – the next step in the process of developing new human therapies.

"Families and advocates are very pleased to see the advancement of this
antisense technology for the treatment of spinal muscular atrophy.  We
have high hopes for the success of the next phase of the work", said Cynthia
Joyce, Executive Director of the SMA Foundation, an advocacy group that provides financial support for this project at CSHL.

The results of the research led by Krainer are published on March 13, 2007 by PLoS Biology:

The paper’s full citation is as follows:
Hua Y, Vickers TA, Baker BF, Bennett CF, Krainer AR (2007) Enhancement of SMN2 exon 7 inclusion by antisense oligonucleotides targeting the exon. PLoS Biol 5(4): e73. doi:10.1371/journal.pbio.0050073

Adrian Krainer is available for comment at This e-mail address is being protected from spambots. You need JavaScript enabled to view it
CSHL is a private, non-profit research and education institution dedicated to exploring molecular biology and genetics in order to advance the understanding and ability to diagnose and treat cancers, neurological diseases, and other causes of human suffering.  For more information visit

About Spinal Muscular Atrophy
Spinal muscular atrophy is a genetic disease that causes the degeneration of spinal cord motor neurons and leads to progressive muscle weakness, atrophy and inability to walk or sit, and breathing difficulties.  Children afflicted with this disease suffer a premature death due to respiratory failure, generally before reaching two years of age.  The SMA Foundation estimates that currently over 50,000 people suffer from SMA in the U.S., Europe and Japan and that a conservative annual market potential for an SMA treatment could exceed $500 million.

About the Spinal Muscular Atrophy Foundation
The Spinal Muscular Atrophy Foundation is a nonprofit organization dedicated to accelerating progress towards a treatment and cure for spinal muscular atrophy through targeted funding of clinical research and novel drug development efforts.  Since 2003, the Foundation has awarded over $30 million in sponsored research agreements.  In addition, the Foundation is committed to raising awareness and generating support for increased research efforts in SMA among the leaders of industry and government.  For more information visit or call (646) 253-7100.

For more information, visit
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