Featured Research

from universities, journals, and other organizations

Gene Therapy For Muscular Dystrophy Fixes Frail Muscle Cells In Animal Model, Stanford Study Finds

Date:
December 27, 2005
Source:
Stanford University Medical Center
Summary:
A new gene therapy technique that has shown promise in skin disease and hemophilia might one day be useful for treating muscular dystrophy, according to a new study by researchers at Stanford University School of Medicine.

A new gene therapy technique that has shown promise in skin disease and hemophilia might one day be useful for treating muscular dystrophy, according to a new study by researchers at Stanford University School of Medicine.

In the study, scheduled to be published online in the Proceedings of the National Academy of Sciences the week of Jan. 2, the researchers used gene therapy to introduce a healthy copy of the gene dystrophin into mice with a condition that mimics muscular dystrophy. The dystrophin gene is mutated and as a result produces a defective protein in the roughly 20,000 people in the United States with the most common form of the disease.

Using gene therapy to treat muscular dystrophy isn't a new idea. Thomas Rando, MD, PhD, associate professor of neurology and neurological sciences, said that researchers have tried several different techniques with variable success. One hurdle is getting genes into muscle cells all over the body. Another is convincing those cells to permanently produce the therapeutic protein made by those genes.

The gene therapy technique Rando and postdoctoral fellow Carmen Bertoni, PhD, used was developed by Michele Calos, PhD, associate professor of genetics. One of the main advantages of this method is that it could potentially provide a long-term fix for a variety of genetic diseases, including muscular dystrophy.

In muscular dystrophy, the muscle cells break down and are slowly replaced by fat. Eventually people with the disease are confined to a wheelchair and usually die in their 20s. There is currently no effective treatment for the disease, which explains why gene therapy remains a hope despite the significant hurdles.

Rando said the PNAS paper highlights an additional requirement for any gene therapy to be successful: the introduced gene must produce healthy dystrophin protein in large quantities in order to repair the entire muscle cell. Previous muscular dystrophy gene therapy studies did not look at whether the introduced dystrophin spread along the entire length of the muscle cell, which can be many millimeters long in mice or inches long in humans.

In the upcoming paper Bertoni used a standard gene therapy method to introduce two genes - dystrophin and a gene that makes a glowing protein - into mice with a mouse version of muscular dystrophy. She found that in mice producing insufficient dystrophin, she could see the glowing protein slowly leak out of the cell. This leakiness is a sign that the cell is not healed. In contrast, when she used Calos' gene therapy technique to introduce the genes, the muscle cell contained high levels of dystrophin distributed along the length of the cell and the glowing protein stayed within the cell, suggesting that the abundant dystrophin repaired the ailing muscle.

"If you have a single cell that's a foot long and you only correct a few inches, you've done very little," Rando said, "Whereas if you correct it from end to end, you truly cure the disease in that cell."

Both Rando and Calos point out that the road to a gene therapy cure for muscular dystrophy is still a long one. However, Calos is confident that her technique will be a part of the journey towards a cure for the disease and for other diseases such as hemophilia and the skin disease, epidermolysis bullosa. Early trials using her approach have looked promising in animal models of both of these diseases.

"I think our approach has a lot of potential to overcome issues that have slowed the field of gene therapy," Calos said.

Calos said her approach has two advantages: one is that in her method the gene gets inserted directly into the cell's own DNA, which is why the correction is permanent. In some other methods the gene stays outside the DNA and slowly breaks down. The second advantage is that her method doesn't rely on a virus to disperse the DNA and therefore avoids some of the issues, including cancer and an immune reaction, that have turned up in viral gene therapy trials. Instead this approach uses naked DNA that travels through the bloodstream to cells of the body.

For his part, Rando said that no matter how well gene therapy works in an isolated muscle, researchers still must figure out how to get that gene to muscles throughout the body. Despite the remaining hurdles, both Rando and Calos said that their study is a step towards eventually treating muscular dystrophy and other diseases using gene therapy.

###

Other researchers who contributed to this work include research assistants Sohail Jarrahian and Yining Li, postdoctoral scholar Thurman Wheeler, MD, and graduate student Eric Olivares, PhD. The project was supported by grants from the Muscular Dystrophy Association.

Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.


Story Source:

The above story is based on materials provided by Stanford University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Stanford University Medical Center. "Gene Therapy For Muscular Dystrophy Fixes Frail Muscle Cells In Animal Model, Stanford Study Finds." ScienceDaily. ScienceDaily, 27 December 2005. <www.sciencedaily.com/releases/2005/12/051227110148.htm>.
Stanford University Medical Center. (2005, December 27). Gene Therapy For Muscular Dystrophy Fixes Frail Muscle Cells In Animal Model, Stanford Study Finds. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2005/12/051227110148.htm
Stanford University Medical Center. "Gene Therapy For Muscular Dystrophy Fixes Frail Muscle Cells In Animal Model, Stanford Study Finds." ScienceDaily. www.sciencedaily.com/releases/2005/12/051227110148.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) — Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
Possible Ebola Patient in Isolation at California Hospital

Possible Ebola Patient in Isolation at California Hospital

Reuters - US Online Video (Aug. 20, 2014) — A patient who may have been exposed to the Ebola virus is in isolation at the Kaiser Permanente South Sacramento Medical Center. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Reasons Why Teen Birth Rates Are At An All-Time Low

Reasons Why Teen Birth Rates Are At An All-Time Low

Newsy (Aug. 20, 2014) — A CDC report says birth rates among teenagers have been declining for decades, reaching a new low in 2013. We look at several popular explanations. Video provided by Newsy
Powered by NewsLook.com
Common Antibiotic Could Lead To Heart-Related Death

Common Antibiotic Could Lead To Heart-Related Death

Newsy (Aug. 20, 2014) — Danish researchers discovered patients taking clarithromycin have an increased risk of dying from a heart-related issue. 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