Navigation Links
Scientists exploring new compounds to target muscular dystrophy
Date:11/19/2008

Scientists have identified a promising set of new compounds in the fight against muscular dystrophy.

Using a drug-discovery technique in which molecules compete against each other for access to the target the strand of toxic RNA that causes the most common form of muscular dystrophy in adults a team at the University of Rochester Medical Center has identified several compounds that, in the laboratory, block the unwanted coupling of two molecules that is at the root of the disease.

The work was published online November 7 by the Journal of the American Chemical Society.

"This discovery gives us, for the first time, a molecule that targets the wayward RNA at the root of myotonic muscular dystrophy," said Benjamin Miller, Ph.D., the chemist who led the study. "This is a first step toward developing a drug-like molecule that perhaps could be used someday to treat the disease. This lead molecule provides a framework for moving forward."

Miller leads a team that is developing small molecules that target small strands of RNA. He notes that drugs more commonly target proteins or DNA, but that RNA offers an alluring target for some diseases.

"The drug discovery field really is wide open when it comes to RNA, which is a very difficult molecule to target," said Miller, who is an associate professor in the departments of Dermatology, Biomedical Engineering, and Biochemistry and Biophysics.

The work is the latest in a series of developments in which a Rochester team led by neurologist Charles Thornton, M.D., has shown how a genetic flaw creates the symptoms of myotonic dystrophy, which affects about 35,000 Americans.

"This is an important first step toward developing a drug treatment for myotonic dystrophy. The message from our patients is loud and clear push this forward as fast as possible," said Thornton, who is co-director of University's Neuromuscular Disease Center.

The disease is marked by progressive muscle weakness, and eventually many patients have difficulty walking, swallowing, and breathing. The disease also affects the eyes, the heart, and the brain. Currently there is no treatment.

The genetic mistake involves a repeated sequence of three chemical bases. Healthy people have anywhere from five to 30 copies of the "triplet repeat" known as CUG on chromosome 19, but people with the disease typically have hundreds or thousands of copies, a kind of molecular stutter. These extra copies become part of large, faulty messenger RNA molecules that can mistakenly glom onto proteins and knockout their normal function.

Earlier this decade, Thornton's team discovered that the faulty messenger RNA has a toxic effect on muscle and heart tissue. The team found that the toxic RNA binds tightly to a crucial protein known as "muscle blind" or MBNL1 and prevents that protein from performing its usual function, ultimately leading to the muscle symptoms of muscular dystrophy.

The goal for doctors is to free up MBNL1 in cells so that it can go about its normal activities, which include building proper chloride channels that are central to normal muscle function.

So Miller set out to free MBNL1 by designing an experiment to search for a small molecule that would sop up extra CUG copies. Using a technique known as dynamic combinatorial chemistry, Miller mixed two sets of 150 compounds, one on polymer beads and the other in solution, and let the components link up with each other in a kind of molecular dance, amid a sea of CUG "triplet repeat" RNA strands. The technique, which Miller helped to pioneer more than a decade ago, allowed him to simultaneously analyze how effectively more than 11,000 molecular combinations could bind to the target CUG RNA strand.

Miller's team sorted out which combinations muscled out the others for access to RNA strands and held most tightly onto them. The team then took the best performers and put them in a solution containing both CUG repeat RNA and MBNL1. Miller's molecules were able to break up the interaction between the two, with the best molecules freeing up to half the MBNL1 the precise step that needs to be taken in patients with the disease.

The team is continuing its work, further refining the molecules in an attempt to find one that frees MBNL1 even more effectively.


'/>"/>

Contact: Tom Rickey
tom_rickey@urmc.rochester.edu
585-275-7954
University of Rochester Medical Center
Source:Eurekalert

Related medicine news :

1. Portuguese scientists discover new mechanism that regulates formation of blood vessels
2. UCLA scientists find cell pathway driving a deadly sub-type of breast cancer
3. Leading Scientists From Around the World Headed to Kansas for Symposium on Combating Deadly Infectious Diseases
4. Cardiff scientists study acute infection in end-stage kidney disease patients
5. Scientists Unravel Mystery of Tamoxifen Resistance
6. Freezing Ovaries Preserves Fertility, Scientists Report
7. TSODs Frank Whyte Provides Negotiation Skills Training to NIH Scientists
8. Scientists Debate Dietary Supplements and Cancer Risk at AICR Conference
9. Penn scientists show how body determines optimal amount of germ-fighting B cells
10. Penn scientists map molecular regulation of fat-cell genetics
11. Scientists Make Clones of Mice Dead 16 Years
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/31/2016)... PA (PRWEB) , ... May 31, 2016 , ... More ... Philadelphia, Hep B United Philadelphia, and the Prevent Cancer Foundation held an event on ... silent epidemic in the city of viral hepatitis, the leading cause of liver cancer. ...
(Date:5/31/2016)... ... May 31, 2016 , ... Splashtop Inc., the worldwide leader in ... Networks Co., the leading provider of secure mobile remote access solution for Japan ... leading CACHATTO remote access solution. Splashtop for CACHATTO will be available as ...
(Date:5/31/2016)... ... ... Twenty years ago it was revolutionary: enabling the people who hear distressing voices ... But this approach has proven transformative, both for people who hear voices and for ... is used around the world, but it still lags in the United States. , ...
(Date:5/31/2016)... ... May 31, 2016 , ... When ... he knew it was something that contractors should have at their disposal on ... gets,” says Butch, CertainTeed’s Director of Contractor Programs. , As a result, ...
(Date:5/31/2016)... ... May 31, 2016 , ... CallTrackingMetrics's software ... campaigns, to monitor the performance of sales and support staff, and to efficiently ... The software allows customers to record, transcribe, route, document, and report on everything ...
Breaking Medicine News(10 mins):
(Date:5/26/2016)... 26, 2016 According to a new ... Market - U.S. Industry Analysis, Size, Share, Growth, Trends, and ... the U.S. was valued at US$ 5.89 Bn in 2014 ... from 2015 to 2023 to reach US$ 7.99 Bn in ... and emerging needle free drug delivery devices and the market ...
(Date:5/26/2016)... 26, 2016 TARE (Transarterial ... Cost Savings and Overall Decreased Use of ... an international specialist healthcare company, has today announced ... Annual Meeting of ISPOR (International Society for Pharmacoeconomics ... carcinoma (HCC) using yttrium-90 glass microspheres is associated ...
(Date:5/26/2016)... , May 26, 2016 ... has matured into an essential life science tool for ... development applications. BCC Research reveals in its new report ... second growth phase, one powered by a range of ...      (Logo: http://photos.prnewswire.com/prnh/20140723/694805 ) , ...
Breaking Medicine Technology: