Research reports from Northwestern University, Research Center provide new insights into spinal muscular atrophy therapy
2007 OCT 8 -- A new study, 'SMN transcript stability: could modulation of messenger RNA degradation provide a novel therapy for spinal muscular atrophy,' is now available. According to recent research from the United States, "Proximal spinal muscular atrophy is caused by deletion or mutation of the survival motor neuron 1 gene, SMN1. Rentention of a nearly identical copy gene, SMN2, enables survival but is unable to fully compensate for the loss of SMN1." "The SMN1 and SMN2 genes differ by a single nucleotide that results in alternative splicing of SMN2 exon 7 due to the disruption of a binding site for an essential splicing factor. This alternatively spliced form encodes a partially functional truncated protein. Because SMN2 is present in patients with spinal muscular atrophy, it is an ideal therapeutic target. Some of the current approaches to increase SMN protein levels are aimed at increasing the transcription from SMN2 or at preventing exon 7 skipping. One area that has yet to be investigated is the stability of messenger ribonucleic acid (RNA) transcripts produced from SMN2. We postulated that transcripts derived from SMN2 may be less stable because alternative splicing, recruitment of RNA-binding proteins, and alteration of stop codons have been associated with changes in rates of messenger RNA decay; these features are all characteristic of SMN2. Accordingly, transcript degradation was examined within primary fibroblast cells that exclusively contained SMN1 or SMN2 by treating cultures with a transcriptional inhibitor to observe messenger RNA stability," wrote C.R. Heier and colleagues, Northwestern University, Research Center. The researchers concluded: "The results indicate that SMN transcript instability does not play a role in the disease mechanism, suggesting that therapeutic modulation of messenger RNA degradation would not target a molecular defect in patients with spinal muscular atrophy, although it could provide general benefits by increasing total pools of SMN2 transcripts.'." Heier and colleagues published their study in the Journal of Child Neurology (SMN transcript stability: could modulation of messenger RNA degradation provide a novel therapy for spinal muscular atrophy? Journal of Child Neurology, 2007;22(8):1013-8). For additional information, contact C.R. Heier, Feinberg School of Medicine, Dept. of Pediatrics, Northwestern University, Human Molecular Genetics Program, Children's Memorial Research Center, Chicago, Illinois USA.. Publisher contact information for the Journal of Child Neurology is: B C Decker Inc., 20 Hughson St. South, PO Box 620, L C D 1, Hamilton, Ontario L8N 3K7, Canada. Keywords: United States, Chicago, Spinal Muscular Atrophy Therapy, Charcot-Marie-Tooth Disease, Child Neurology, Drug Development, Neurology, Pharmaceuticals, Spinal Muscular Atrophy, Therapy, Treatment. This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.
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