Featured Research

from universities, journals, and other organizations

First clinical trial of gene therapy for muscular dystrophy lends insight into the disease

Date:
October 7, 2010
Source:
University of North Carolina School of Medicine
Summary:
A clinical trial designed to replace the genetic defect causing the most common form of muscular dystrophy has uncovered an unexpected aspect of the disease. The trial showed that some patients mount an immune response to the dystrophin protein even before they have received the gene therapy.

A clinical trial designed to replace the genetic defect causing the most common form of muscular dystrophy has uncovered an unexpected aspect of the disease. The trial, based on therapy designed by scientists at the University of North Carolina at Chapel Hill School of Medicine, showed that some patients mount an immune response to the dystrophin protein even before they have received the gene therapy.

The puzzling results, which came from trials at Columbus Children's Hospital in Ohio, suggest that the immune systems of a number of patients -- once thought to be completely devoid of the dystrophin protein -- are actually primed by the prior existence of tiny amounts of this important component of muscle.

Published in the New England Journal of Medicine, the study demonstrates how such careful and critical observation in early clinical trials of new therapies can yield new insights into the causes of even the "simplest" single gene disorders.

"These findings are going to be studied intensely going forward, and should help us to understand how to better tailor our treatment approaches to suit the patients' needs," said study author R. Jude Samulski, professor of pharmacology and director of the Gene Therapy Center at UNC.

Duchenne muscular dystrophy is a genetic disease that begins in early childhood, causes progressive muscle weakness, and usually leads to death by the age of twenty from respiratory or cardiac muscle failure. The illness, which primarily affects boys, occurs when a gene on the X chromosome fails to make the essential muscle protein dystrophin. Currently, the best medical therapy can only slow its progression.

The use of gene therapy to correct such single gene disorders has been explored for over two decades and has been met with a number of challenges. In the case of muscular dystrophy, the dystrophin gene is far too large to fit into the typical virus used to carry it into the patient's cells. So collaborator Xiao Xiao, PhD from UNC Eshelman School of Pharmacy engineered a smaller yet functional version of the gene -- called a minigene -- to place within the viral carrier. His virus of choice was adeno-associated virus or AAV, a small virus that most humans are exposed to at some point in life.

In the first trial of this form of gene therapy, which began in 2006, six boys with muscular dystrophy received the virus containing the dystrophin minigene. A phase I trial, the goals of the study were to assess the efficacy and safety of the new approach. The replacement genes were injected into the bicep in one arm and a placebo was injected into the other arm of each of the patients.

The researchers found that the immune response to the gene varied from patient to patient, perhaps in part because the patients harbored different amounts of "revertant" dystrophin fibers, fibers that have escaped the fate of their mutation. Further studies are needed, but this finding suggests that some patients may benefit from immunosuppression prior to receiving gene therapy.

"We can now use this new information to adapt our approach to make gene therapy more likely to succeed," said Samulski. "Right now we are searching for a way to cure this disease, not just care for it, but truly cure it. So we realize that this effort is going to be an iterative process, with the accumulation of a number of lessons along the way to help us succeed."

One lesson from this study suggests that keeping a close eye on the immune-response profiles of patients could help to enhance the success of not just gene therapy, but also other therapies aimed at restoring dystrophin activity.

The research was funded in part by the Muscular Dystrophy Association and UNC startup biotech company Asklepios BioPharmaceutical Inc. Study co-authors from UNC include Dawn Bowles, PhD; Steven Gray, PhD; Chengwin Li, PhD; and Xiao Xiao, PhD.


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. Jerry R. Mendell, Katherine Campbell, Louise Rodino-Klapac, Zarife Sahenk, Chris Shilling, Sarah Lewis, Dawn Bowles, Steven Gray, Chengwen Li, Gloria Galloway, Vinod Malik, Brian Coley, K. Reed Clark, Juan Li, Xiao Xiao, Jade Samulski, Scott W. McPhee, R. Jude Samulski, Christopher M. Walker. Dystrophin Immunity in Duchenne's Muscular Dystrophy. New England Journal of Medicine, 2010; 363 (15): 1429 DOI: 10.1056/NEJMoa1000228

Cite This Page:

University of North Carolina School of Medicine. "First clinical trial of gene therapy for muscular dystrophy lends insight into the disease." ScienceDaily. ScienceDaily, 7 October 2010. <www.sciencedaily.com/releases/2010/10/101006175630.htm>.
University of North Carolina School of Medicine. (2010, October 7). First clinical trial of gene therapy for muscular dystrophy lends insight into the disease. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2010/10/101006175630.htm
University of North Carolina School of Medicine. "First clinical trial of gene therapy for muscular dystrophy lends insight into the disease." ScienceDaily. www.sciencedaily.com/releases/2010/10/101006175630.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 Video provided by AFP
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