Featured Research

from universities, journals, and other organizations

Clinical trial of molecular therapy for muscular dystrophy yields significant positive results

Date:
July 26, 2011
Source:
University of North Carolina School of Medicine
Summary:
A molecular technique has taken one step closer to becoming a treatment for the devastating genetic disease Duchenne muscular dystrophy.

A molecular technique originally developed at the University of North Carolina at Chapel Hill has taken one step closer to becoming a treatment for the devastating genetic disease Duchenne muscular dystrophy.

Related Articles


The novel treatment uses strips of genetic code -- called antisense oligonucleotides -- to restore the function of a defective dystrophin gene. In a study published July 25, 2011 in the journal The Lancet, researchers from the U.K., U.S. and Australia demonstrated that a phase Ib/IIa trial of the approach restored production of the critical muscle protein missing in patients with the progressive neuromuscular condition.

"When I first tried my approach in a test tube some twenty years ago, a reviewer of my manuscript commented that it was 'molecular gymnastics that will never amount to anything,'" said study author Ryszard Kole, PhD, a professor of pharmacology who has taken a leave of absence from UNC to develop the technology with AVI Biopharma, in Bellevue, Washington. "Now we have evidence that it works, and in an illness that has no other good therapeutic options."

Duchenne muscular dystrophy is a lethal disease that affects 1 in 3500 newborn boys. In the disease, omissions or misprints in the letters of the dystrophin gene cause its "reading frame" to shift, abbreviating the instructions for making the dystrophin protein. As a result, the cells fail to make a functional muscle protein and patients eventually lose their ability to walk and breathe. In a milder form of the disease, called Becker muscular dystrophy, the genetic defect leads to one missed component but leaves the rest intact, resulting in a muscle protein that is largely functional and patients that can have a normal lifespan.

In the current study, the researchers tested a way to turn the lethal to the livable form of the illness by using antisense oligonucleotides, strings of genetic lettering that can stick to and mask sections of code. The oligonucleotides cause the cell's "splicing" machinery -- responsible for cutting and pasting the instructions together -- to skip a few paragraphs so the reading frame is back on track and the rest of the dystrophin protein can be made as instructed.

To prove this concept, the scientists administered the treatment intraveneously (IV) to 19 Duchenne muscular dystrophy patients over the course of 12 weeks. They found that the drug was well tolerated and appeared to increase the levels of dystrophin protein in a statistically significant dose-dependent manner. The best 3 responders showed an increase following treatment of protein levels from 2 percent to 18 percent, from 0.9 percent to17 percent and from 0 percent to 7.7 percent of normal muscle, respectively.

They now plan to expand their studies in a next trial, increasing both the dose and the duration of the treatment to see if the approach has clinical impact. In the future the researchers would like to develop alternative formulations of the drug that can be administered subcutaneously, like for diabetes, or perhaps even in pill form. But Kole says even the current approach holds great promise for the over 30,000 people who have the illness worldwide.

"If I get to see one child benefit from this treatment, it will be a life as a scientist well spent," said Kole.

The research was funded in part by the National Institute of General Medical Sciences and the National Heart, Lung and Blood Institute.


Story Source:

The above story is based on materials provided by University of North Carolina School of Medicine. Note: Materials may be edited for content and length.


Journal Reference:

  1. Sebahattin Cirak, Virginia Arechavala-Gomeza, Michela Guglieri, Lucy Feng, Silvia Torelli, Karen Anthony, Stephen Abbs, Maria Elena Garralda, John Bourke, Dominic J Wells, George Dickson, Matthew JA Wood, Steve D Wilton, Volker Straub, Ryszard Kole, Stephen B Shrewsbury, Caroline Sewry, Jennifer E Morgan, Kate Bushby, Francesco Muntoni. Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study. The Lancet, 2011; DOI: 10.1016/S0140-6736(11)60756-3

Cite This Page:

University of North Carolina School of Medicine. "Clinical trial of molecular therapy for muscular dystrophy yields significant positive results." ScienceDaily. ScienceDaily, 26 July 2011. <www.sciencedaily.com/releases/2011/07/110725123409.htm>.
University of North Carolina School of Medicine. (2011, July 26). Clinical trial of molecular therapy for muscular dystrophy yields significant positive results. ScienceDaily. Retrieved January 29, 2015 from www.sciencedaily.com/releases/2011/07/110725123409.htm
University of North Carolina School of Medicine. "Clinical trial of molecular therapy for muscular dystrophy yields significant positive results." ScienceDaily. www.sciencedaily.com/releases/2011/07/110725123409.htm (accessed January 29, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Thursday, January 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Malnutrition on the Rise as Violence Flares in C. Africa

Malnutrition on the Rise as Violence Flares in C. Africa

AFP (Jan. 28, 2015) Violence can flare up at any moment in Bambari with only a bridge separating Muslims and Christians. Malnutrition is on the rise and lack of water means simple cooking fires threaten to destroy makeshift camps where people are living. Duration: 00:40 Video provided by AFP
Powered by NewsLook.com
Poultry Culled in Taiwan to Thwart Bird Flu

Poultry Culled in Taiwan to Thwart Bird Flu

Reuters - News Video Online (Jan. 28, 2015) Taiwan culls over a million poultry in efforts to halt various strains of avian flu. Julie Noce reports. Video provided by Reuters
Powered by NewsLook.com
Media Criticizing Parents For Not Vaccinating Children

Media Criticizing Parents For Not Vaccinating Children

Newsy (Jan. 28, 2015) As the Disneyland measles outbreak continues to spread, the media says parents who choose not to vaccinate their children are part of the cause. Video provided by Newsy
Powered by NewsLook.com
Shark Bite Victim Making Amazing Recovery

Shark Bite Victim Making Amazing Recovery

AP (Jan. 27, 2015) A Texas woman who lost more than five pounds of flesh to a shark in the Bahamas earlier this month could be released from a Florida hospital soon. Experts believe she was bitten by a bull shark while snorkeling. (Jan. 27) Video provided by AP
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