Featured Research

from universities, journals, and other organizations

New molecule heralds hope for muscular dystrophy treatment

Date:
May 1, 2013
Source:
University of Illinois at Urbana-Champaign
Summary:
There's hope for patients with myotonic dystrophy, the most common form of muscular dystrophy in adults. A new small molecule has been shown to break up the protein-RNA clusters that cause the disease in living human cells, an important first step toward developing a pharmaceutical treatment for the as-yet untreatable disease.

In myotonic dystrophy, a mutation causes RNA to bind to an important protein in the cell nucleus. A new molecule developed at the University of Illinois causes the RNA to "let go" of the protein, breaking up the nuclear clusters.
Credit: Graphic by Amin Haghighat Jahromi

There's hope for patients with myotonic dystrophy. A new small molecule developed by researchers at the University of Illinois has been shown to break up the protein-RNA clusters that cause the disease in living human cells, an important first step toward developing a pharmaceutical treatment for the as-yet untreatable disease.

Related Articles


Steven C. Zimmerman, the Roger Adams Professor of Chemistry at the U. of I., led the group in developing and demonstrating the compound. The National Institutes of Health supported the work published in the journal ACS Chemical Biology.

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults, affecting one in 8,000 people in North America. It causes progressive weakness as the muscles deteriorate over time. There is no treatment available for the disease; though a few measures can help ease some symptoms, nothing can halt their inevitable progression.

"This is a disease that currently doesn't have any treatment, so we have a huge interest in finding therapeutic agents," said graduate student Amin Haghighat Jahromi, the first author of the paper.

Myotonic dystrophy type 1, called DM1 for short, is caused by a mutation to one gene. In a healthy person, one small segment of the gene -- a DNA sequence of CTG -- is repeated a few times. In someone with DM1, the sequence is repeated more than 50 times, even up to thousands of repeats. The sequence is transcribed into RNA over and over, like a skipping record stuck in a loop. The repetitive RNA binds to the protein MBNL1, which is essential for regulating protein balance in cells. The RNA traps the MBNL1 protein in aggregates within the cell's nucleus.

"The RNA is functioning in an abnormal way, and unfortunately, it's toxic," Zimmerman said. "MNBL regulates a process called alternative splicing that controls how much of different proteins are made. Affected cells make the proteins, just not at the right levels, so all the levels are imbalanced. There are more than 100 proteins that are affected."

The Illinois group developed a small molecule that could infiltrate the nucleus and bind to the RNA, forcing it to let go of MBNL1 so the protein can do its job. The molecule is small and water-soluble so it can cross the membrane into the cell, which has been a challenge for researchers attempting to use methods with larger molecules. It specifically targets only the repeating RNA sequence so as not to interfere with other cellular functions.

The researchers administered the molecule to live cells that have the disease features of DM1. Using advanced microscopy methods, they were able to watch the cells over time to see how they responded to the molecule. In only a few hours, they saw the clusters within the nucleus break up and were able to measure that the MBNL1 protein had increased its regulatory activity.

"This is the first study that gives direct evidence for the function of the compound," Jahromi said. "We track how the cell is changing upon treatment with the compound and see the effect directly."

Next, the researchers plan to begin collaborating with other groups to test their molecule in fruit flies and mice. Although the molecule will need many rounds of testing for toxicity, efficacy, metabolism and possible side effects before human trials can begin, finding a molecule that works in living cells is an important first step toward making a drug that could treat myotonic dystrophy.

"We're close to developing drug candidates that can be tested in animals. And if it works in animals, then we move hopefully into clinical trials with humans," Zimmerman said. "It's heartbreaking, at one level, to say we're years away from something that's going to be in the clinic. On the other hand, we now have targets. We now know how to go after this disease. It gives patients and their families a bit of hope."


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Journal Reference:

  1. Amin Haghighat Jahromi, Lien Nguyen, Yuan Fu, Kali A. Miller, Anne M. Baranger, Steven C. Zimmerman. A Novel CUGexp·MBNL1 Inhibitor with Therapeutic Potential for Myotonic Dystrophy Type 1. ACS Chemical Biology, 2013; 130320091510009 DOI: 10.1021/cb400046u

Cite This Page:

University of Illinois at Urbana-Champaign. "New molecule heralds hope for muscular dystrophy treatment." ScienceDaily. ScienceDaily, 1 May 2013. <www.sciencedaily.com/releases/2013/05/130501145107.htm>.
University of Illinois at Urbana-Champaign. (2013, May 1). New molecule heralds hope for muscular dystrophy treatment. ScienceDaily. Retrieved November 25, 2014 from www.sciencedaily.com/releases/2013/05/130501145107.htm
University of Illinois at Urbana-Champaign. "New molecule heralds hope for muscular dystrophy treatment." ScienceDaily. www.sciencedaily.com/releases/2013/05/130501145107.htm (accessed November 25, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, November 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

From Popcorn To Vending Snacks: FDA Ups Calorie Count Rules

Newsy (Nov. 25, 2014) — The US FDA is announcing new calorie rules on Tuesday that will require everywhere from theaters to vending machines to include calorie counts. Video provided by Newsy
Powered by NewsLook.com
Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Daily Serving Of Yogurt Could Reduce Risk Of Type 2 Diabetes

Newsy (Nov. 25, 2014) — Need another reason to eat yogurt every day? Researchers now say it could reduce a person's risk of developing type 2 diabetes. Video provided by Newsy
Powered by NewsLook.com
Madagascar Working to Contain Plague Outbreak

Madagascar Working to Contain Plague Outbreak

AFP (Nov. 24, 2014) — Madagascar said Monday it is trying to contain an outbreak of plague -- similar to the Black Death that swept Medieval Europe -- that has killed 40 people and is spreading to the capital Antananarivo. Duration: 00:42 Video provided by AFP
Powered by NewsLook.com
Are Female Bosses More Likely To Be Depressed?

Are Female Bosses More Likely To Be Depressed?

Newsy (Nov. 24, 2014) — A new study links greater authority with increased depressive symptoms among women in the workplace. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins