Public Release:  New hope exists in treating inherited disease by suppressing DNA mutations

Federation of American Societies for Experimental Biology

ANAHEIM, CA - Genetic mutation can disrupt the way human cells make proteins, which in turn leads to inherited disease. David Bedwell, a professor in the University of Alabama at Birmingham (UAB) Department of Microbiology, says scientists are closer than ever to producing drugs that fix this disrupted-protein pathway and drastically improving treatment of genetic disease.

Bedwell is a renowned researcher on a select group of genetic alterations called nonsense mutations - DNA alterations that can lead to nonfunctional or missing proteins. He will present a lecture on Monday, April 26, at 9:55 am PST in Anaheim Convention Center Room 304B.

His talk, "Pharmacological suppression of nonsense mutations to treat genetic diseases," examines the promise of Bedwell's groundbreaking research on the experimental drug ataluren (formerly called PTC124) that may help to treat some cystic fibrosis patients. Ataluren also holds promise in treating more than 2,400 different genetic disorders caused by nonsense mutations.

"When treating a genetic disease with suppression therapy, the key consideration is the fraction of the missing protein that must be restored to yield a therapeutic benefit," Bedwell says. "It comes down to the threshold of protein rescue needed. For some diseases, it might be one percent of the normal amount of protein that must be restored, and for other diseases, you may need 50 percent of protein restored."

In Bedwell's most well-known study, ataluren restored up to 29 percent of normal protein function in mice with cystic fibrosis. Another researcher not affiliated with UAB has reported ataluren restored up to 25 percent of the missing or abnormal protein function in mice with Duchenne muscular dystrophy.

An estimated one-third of gene defects responsible for human disease are thought to come from nonsense mutations. In the case of cystic fibrosis, the absence of a certain protein leads to an imbalance of salt and water in the linings of the lungs and other membranes. The UAB study showed that ataluren allowed the protein to be made in mouse cells where it was previously absent, and it helped the body's regulatory system to restore salt and water balance in the membrane.

Bedwell says the true promise of drugs that suppress nonsense mutations is their selectiveness, meaning the drugs work well to suppress disease-causing mutations while generally sparing healthy genes.

Ataluren is now being tested in humans for its effectiveness in treating Duchenne/Becker muscular dystrophy, cystic fibrosis, hemophilia A, hemophilia B and other conditions. The agent works in an oral form.

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The UAB research is funded by PTC Therapeutics, Inc. with assistance from the National Institutes of Health.

Note: Bedwell reports a consulting relationship with ataluren-maker PTC Therapeutics.

NOTE TO EDITORS: The American Society for Biochemistry and Molecular Biology annual meeting is part of the Experimental Biology 2010 conference that will be held April 24-28, 2010 at the Anaheim Convention Center. The press is invited to attend or to make an appointment to interview Dr. Bedwell. Please contact Nicole Kresge at 202.316.5447 or nkresge@asbmb.org.

The American Society for Biochemistry and Molecular Biology (www.asbmb.org) is a nonprofit scientific and educational organization with over 12,000 members. Founded in 1906, the Society is based in Bethesda, Maryland, on the campus of the Federation of American Societies for Experimental Biology. The Society's purpose is to advance the science of biochemistry and molecular biology through publication of scientific and educational journals: the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research, organization of scientific meetings, advocacy for funding of basic research and education, support of science education at all levels, and promoting the diversity of individuals entering the scientific workforce.

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