ScienceDaily (Dec. 19, 2008) — Spinal muscular atrophy, a neurodegenerative disorder that causes the weakening of muscles, is the leading cause of infant death and occurs in 1 in 6,000 live births.  While trans-splicing (a form of molecular therapy) has had impressive results as a treatment for spinal muscular atrophy in cell-based models of disease, scientists have been unable to translate the therapy to the human body.

A University of Missouri researcher has developed a strategy that will enhance trans-splicing activity and bring it closer to being used in the clinical setting.

Spinal muscular atrophy is caused by the loss of survival motor neuron-1(SMN1). In humans, a nearly identical copy gene is present called SMN2. Because of a single molecular difference, SMN2 alone cannot compensate for the loss of SMN1, but it can be used as a primary target for therapeutics, including trans-splicing. Trans-splicing therapy relies on splicing, or uniting, of mutant RNA and therapeutic RNA in order to correct RNA sequence.

To improve efficiency, the researchers developed a trans-splicing system that uses a strand of RNA that can bind to a gene and inactivate it. Turning the gene "off" reduces competition at splice sites and improves the likelihood of achieving the desired results.

"The key to introducing trans-splicing in clinical settings is developing efficient trans-splicing systems," said Chris Lorson, investigator in the Christopher S. Bond Life Sciences Center; associate professor of veterinary pathobiology in the MU College Veterinary Medicine; and scientific director for Fight SMA, a private spinal muscular atrophy research foundation in Richmond, Va. "We have found that reducing the competition between the splice sites enhances the efficiency of trans-splicing. This strategy provides insight into the trans-splicing mechanism and significantly improves trans-splicing activity in a mouse model of spinal muscular atrophy."

Story Source:

Adapted from materials provided by University of Missouri-Columbia.

Journal Reference:

1. Coady et al. Development of a Single Vector System that Enhances Trans-Splicing of SMN2 Transcripts. PLoS ONE, 2008; 3 (10): e3468 DOI: 10.1371/journal.pone.0003468

Related Stories

Possible Treatment For Spinal Muscular Atrophy (July 31, 2009) — Spinal muscular atrophy affects 1 in 6,000 to 1 in 10,000 children born every year. One in 40 people are carriers of the disease -- they don't have the symptoms, but could pass the disease to their ...  > read more

New Insights On Spinal Muscular Atrophy (June 2, 2008) — Researchers have discovered that the effect of a protein deficiency, which is the basis of the neuromuscular disease spinal muscular atrophy, is not restricted to motor nerve cells, suggesting that ...  > read more

Target That Could Ease Spinal Muscular Atrophy Symptoms Discovered (Jan. 12, 2009) — There is no cure for spinal muscular atrophy (SMA), a genetic disorder that causes the weakening of muscles and is the leading genetic cause of infant death, but researchers have discovered a new ...  > read more

Correcting RNA Splicing May Help Treat Spinal Muscular Atrophy (Mar. 13, 2007) — RNA Splicing antisense technology studied at Cold Spring Harbor Laboratory effectively corrected an mRNA splicing defect found in spinal muscular atrophy ...  > read more

Search ScienceDaily

Spinal Cord Injuries: Back on Your Feet