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Small molecule inhibits pathology associated with myotonic dystrophy type 1
Date:9/7/2009

CHAMPAIGN, Ill. Researchers at the University of Illinois have designed a small molecule that blocks an aberrant pathway associated with myotonic dystrophy type 1, the most common form of muscular dystrophy.

The new compound, soon to be tested in cells, binds tightly to its target, an abnormally elongated RNA that hijacks part of the normal cellular machinery and brings on symptoms of the disease. The newly developed compound is the first to show high selectivity in binding the target while not disrupting other important RNA functions. The study appears this week in the Proceedings of the National Academy of Sciences.

Myotonic dystrophy type 1, a muscle degeneration disease that so far is untreatable, affects about one in 8,000 people worldwide. Some cases are mild, but others lead to a debilitating loss of muscle control, declines in organ function and other potentially life-threatening conditions.

Scientists have recently identified a primary causative agent of the disease, a mutant version of a gene, called DMPK, which contains an excessive number of tri-nucleotide repeats. Nucleotides are the chemical letters that spell out the sequence of a gene, and the normal version of the DMPK gene includes five to 34 cytosine-thymine-guanine (CTG) repeats. The mutant version of the gene includes 50 to as many as 10,000 CTG repeats.

"The longer the repeat the worse the disease and the earlier the onset of the disease," said U. of I. chemistry professor and department head Steven Zimmerman, who co-led the research with his colleague, chemistry professor Anne Baranger.

When the mutant DMPK is transcribed into RNA, the first step toward building a protein, these (now CUG) repeats bind to a cellular protein, MBNL, which normally splices other RNA transcripts. The bound MBNL cannot function properly, causing a cascade of negative effects in the cell. Improperly spliced RNAs lead to improperly formed proteins.

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Contact: Diana Yates
diya@illinois.edu
217-333-5802
University of Illinois at Urbana-Champaign
Source:Eurekalert  

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