Featured Research

from universities, journals, and other organizations

Quantum leap in gene therapy of Duchenne muscular dystrophy

Date:
January 15, 2013
Source:
University of Missouri-Columbia
Summary:
For years, scientists have been working to find the key to restoring dystrophin, but they have faced many challenges. After careful evaluation of 22 dogs, researchers found that the new version of the micro-dystrophin gene not only reduced inflammation and fibrosis, it also effectively improved muscle strength.

In the absence of any treatment, the muscle structure is severely damaged. Muscle cell death (rounded cells) and muscle inflammation (blue staining) is abundant.
Credit: University of Missouri

Usually, results from a new study help scientists inch their way toward an answer whether they are battling a health problem or are on the verge of a technological breakthrough. Once in a while, those results give them a giant leap forward. In a preliminary study in a canine model of Duchenne muscular dystrophy (DMD), University of Missouri scientists showed exactly such a leap using gene therapy to treat muscular dystrophy.

The results of the study will be published in the journal Molecular Therapy on Jan. 15, 2013.

Muscular dystrophy occurs when damaged muscle tissue is replaced with fibrous, bony or fatty tissue and loses function. Duchenne muscular dystrophy is the most common type of muscular dystrophy predominantly affecting boys. Patients with DMD have a gene mutation that disrupts the production of dystrophin, a protein essential for muscle cell survival and function. Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. For years, scientists have been working to find the key to restoring dystrophin, but they have faced many challenges.

One of the largest hurdles in DMD gene therapy is the large size of the gene. Dystrophin is the largest gene in the human genome, containing approximately 4,000 amino acids. To fit the dystrophin gene into a vehicle that could deliver the gene to the appropriate site in the body, one has to delete 70 percent of the gene. The highly abbreviated gene is known as the "micro-dystrophin" gene. Previous studies suggest that micro-dystrophin can effectively stop muscle disease in mice that are missing dystrophin. However, mice that are missing dystrophin show minimal DMD symptoms, and results from mice often do not predict what will happen in humans. In contrast to mice, loss of dystrophin results in severe muscular dystrophy in dogs. If micro-dystrophin can work in dystrophic dogs, it will likely work in human patients. Unfortunately, when micro-dystrophin was tested in dogs in previous studies, it was not successful.

To overcome these hurdles, a team led by Dongsheng Duan, the Margaret Proctor Mulligan Professor in Medical Research at the MU School of Medicine, engineered a new micro-dystrophin gene that carries an important functional region missing in previously tested micro-dystrophins.

"We placed the new microgene into a virus and then injected the virus into dystrophic dogs' muscles," Duan said. Following gene therapy, Duan's team examined the dogs for signs of muscle disease and measured muscle force in treated and untreated dogs. After careful evaluation of 22 dogs, Duan and colleagues found that the new version of micro-dystrophin not only reduced inflammation and fibrosis, it also effectively improved muscle strength.

"This is the first time that we have seen positive gene therapy results in large mammals of DMD," said Duan. "We still have a lot of work to do, but we now know that our gene therapy strategy works in large mammals; this is a quantum leap forward in fighting this disease. Our next step is to test our strategy in a large group of muscles in the dogs, and then, eventually, see if 'whole body therapy' will work in the dogs. We are still a long way off before we will have a human treatment, but with this finding, I do see a light at the end of this tunnel."

If additional studies, including animal studies, are successful within the next few years, MU officials would request authority from the federal government to begin human drug development (this is commonly referred to as the "investigative new drug" status). After this status has been granted, researchers may conduct human clinical trials with the hope of developing new treatments for Duchenne muscular dystrophy.


Story Source:

The above story is based on materials provided by University of Missouri-Columbia. Note: Materials may be edited for content and length.


Journal Reference:

  1. Jin-Hong Shin, Xiufang Pan, Chady H Hakim, Hsiao T Yang, Yongping Yue, Keqing Zhang, Ronald L Terjung, Dongsheng Duan. Microdystrophin Ameliorates Muscular Dystrophy in the Canine Model of Duchenne Muscular Dystrophy. Molecular Therapy, 2013; DOI: 10.1038/mt.2012.283

Cite This Page:

University of Missouri-Columbia. "Quantum leap in gene therapy of Duchenne muscular dystrophy." ScienceDaily. ScienceDaily, 15 January 2013. <www.sciencedaily.com/releases/2013/01/130115111748.htm>.
University of Missouri-Columbia. (2013, January 15). Quantum leap in gene therapy of Duchenne muscular dystrophy. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/2013/01/130115111748.htm
University of Missouri-Columbia. "Quantum leap in gene therapy of Duchenne muscular dystrophy." ScienceDaily. www.sciencedaily.com/releases/2013/01/130115111748.htm (accessed September 16, 2014).

Share This



More Health & Medicine News

Tuesday, September 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. Video provided by Newsy
Powered by NewsLook.com
Man Floats for 31 Hours in Gulf Waters

Man Floats for 31 Hours in Gulf Waters

AP (Sep. 16, 2014) A Texas man is lucky to be alive after he and three others floated for more than a day in the Gulf of Mexico when their boat sank during a fishing trip. (Sept. 16) Video provided by AP
Powered by NewsLook.com
EU Ministers and Experts Meet to Discuss Ebola Reponse

EU Ministers and Experts Meet to Discuss Ebola Reponse

AFP (Sep. 15, 2014) The European Commission met on Monday to coordinate aid that the EU can offer to African countries affected by the Ebola outbreak. Duration: 00:58 Video provided by AFP
Powered by NewsLook.com
Despite The Risks, Antibiotics Still Overprescribed For Kids

Despite The Risks, Antibiotics Still Overprescribed For Kids

Newsy (Sep. 15, 2014) A new study finds children are prescribed antibiotics twice as often as is necessary. 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:
from the past week

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