Penn researchers gain new insights on spinal muscular atrophyMay 30, 2008PHILADELPHIA - Researchers from the University of Pennsylvania School of Medicine discovered that the effect of a protein deficiency, which is the basis of the neuromuscular disease spinal muscular atrophy (SMA), is not restricted to motor nerve cells, suggesting that SMA is a more general disorder. This new insight will allow for better understanding of how this complex disease arises. Gideon Dreyfuss, PhD, the Isaac Norris Professor of Biochemistry and Biophysics and Investigator, Howard Hughes Medical Institute and colleagues, report their findings in last week's issue of Cell. SMA is a group of hereditary diseases that causes weakness and wasting of the voluntary muscles in the arms and legs of infants and children. The disorders are a result of genetic lesions in a gene called survival of motor proteins (SMN) that cause a deficiency in the SMN protein. This protein is essential for all cells, but reduced levels of SMN cause spinal muscular atrophy. Why this seemingly cell-specific reduction happens is not known. SMN normally works in all cells to bring small RNAs together with specific proteins to form particles called snRNPs (pronounced snurps). snRNPs are the molecular machines that splice different parts of RNA together to form the messenger RNA (mRNA) before it leaves the nucleus to travel to the cytoplasm. Here, mRNAs get translated into working proteins.
"SMN plays a key role in determining the inventory of the different types of snRNPs in all cells, what we call the snRNP repertoire or the 'snRNPertoire,'" says Dreyfuss. "When SMN levels are reduced, the biochemical balance needed to make the snRNP complexes for splicing RNA is impaired." The Dreyfuss lab looked at reduced SMN levels in cultured cells and mice and found that changes in levels of the snRNPs, as well as the mRNAs - their spliced products - were affected, producing numerous abnormal mRNAs. These effects varied from tissue to tissue. The findings suggest that spinal muscular atrophy is a general disease of splicing. "Now we know that SMA is clearly a disease that not only affects motor neurons, but all cell types when the gene for SMN is damaged," says Dreyfuss. In the end, concludes Dreyfuss, this is a different way to look at the disease. Finding a way to restore SMN levels in the entire body is one therapeutic approach to aim for, based on these findings. University of Pennsylvania School of Medicine | |||||||||||||||||||||
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Related Spinal Muscular Atrophy Current Events and Spinal Muscular Atrophy News Articles Cold Spring Harbor Laboratory Scientists Devise Potential Approach To Treat Spinal Muscular Atrophy In the neuromuscular disease called spinal muscular atrophy, or SMA, a protein deficiency caused by a single gene mutation leads to serious damage in growing nerve cells and the muscles they control. CSHL shows correcting rna splicing may help treat spinal muscular atrophy 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. Treatment extends survival in mouse model of spinal muscular atrophy Drug therapy can extend survival and improve movement in a mouse model of spinal muscular atrophy (SMA), new research shows. The study, carried out at the NIH's National Institute of Neurological Disorders and Stroke (NINDS), suggests that similar drugs might one day be useful for treating human SMA. Drug blocks lethal motor-neuron disease in mice Spinal muscular atrophy (SMA) is an inherited motor-neuron disease that, in its most severe form, leads to death before 2 years of age and for which there is no treatment. Genetic variation: We're more different than we thought New research shows that at least 10 percent of genes in the human population can vary in the number of copies of DNA sequences they contain-a finding that alters current thinking that the DNA of any two humans is 99.9 percent similar in content and identity. Epilepsy drug eases symptoms of inherited disorder that weakens muscles An epilepsy drug that has been on the market for decades can ease the symptoms of adult sufferers with a genetic disorder that seriously weakens muscles. Neurons grown from embryonic stem cells restore function in paralyzed rats For the first time, researchers have enticed transplants of embryonic stem cell-derived motor neurons in the spinal cord to connect with muscles and partially restore function in paralyzed animals. 'Smart' genetic therapy helps the body to heal itself New approaches to genetic disease, based on cells' own ability to correct themselves, will be outlined today (Monday 8 May 2006) at the annual conference of the European Society of Human Genetics in Amsterdam, The Netherlands. Neurological disease raises risk of complications from flu As another flu season approaches, patients with neurological and neuromuscular disease are especially vulnerable to respiratory failure caused by influenza. Scientists discover possible new treatment for genetic diseases Scientists from Imperial College London, the University of Leicester, and Hammersmith Hospital have found a way to stop certain types of genetic diseases from occurring by modifying the way DNA is turned into proteins. The research published in this month's Proceedings of the National Academy of Science shows how the researchers have been able to restore proper expression of defective genes, and that this might potentially have a positive effect in genetic diseases such as spinal muscular atrophy. The research was carried out at Imperial College London and the University of Leicester as a collaboration between Professor Francesco Muntoni and Professor Ian Eperon. Professor Muntoni, from More Spinal Muscular Atrophy Current Events and Spinal Muscular Atrophy News Articles |
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