Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A quantum leap in gene therapy of Duchenne muscular dystrophy

16.01.2013
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.

The study was funded by the National Institutes of Health, Jessey's Journey-The Foundation for Cell and Gene Therapy and the Muscular Dystrophy Association.

Christian Basi | EurekAlert!
Further information:
http://www.missouri.edu

More articles from Health and Medicine:

nachricht Proteomics and precision medicine
08.02.2016 | University of Iowa Health Care

nachricht Scientists create imaging 'toolkit' to help identify new brain tumor drug targets
02.02.2016 | eLife

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The most accurate optical single-ion clock worldwide

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock which attains an accuracy which had only been predicted theoretically so far. Their optical ytterbium clock achieved a relative systematic measurement uncertainty of 3 E-18. The results have been published in the current issue of the scientific journal "Physical Review Letters".

Atomic clock experts from the Physikalisch-Technische Bundesanstalt (PTB) are the first research group in the world to have built an optical single-ion clock...

Im Focus: Goodbye ground control: autonomous nanosatellites

The University of Würzburg has two new space projects in the pipeline which are concerned with the observation of planets and autonomous fault correction aboard satellites. The German Federal Ministry of Economic Affairs and Energy funds the projects with around 1.6 million euros.

Detecting tornadoes that sweep across Mars. Discovering meteors that fall to Earth. Investigating strange lightning that flashes from Earth's atmosphere into...

Im Focus: Flow phenomena on solid surfaces: Physicists highlight key role played by boundary layer velocity

Physicists from Saarland University and the ESPCI in Paris have shown how liquids on solid surfaces can be made to slide over the surface a bit like a bobsleigh on ice. The key is to apply a coating at the boundary between the liquid and the surface that induces the liquid to slip. This results in an increase in the average flow velocity of the liquid and its throughput. This was demonstrated by studying the behaviour of droplets on surfaces with different coatings as they evolved into the equilibrium state. The results could prove useful in optimizing industrial processes, such as the extrusion of plastics.

The study has been published in the respected academic journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Im Focus: New study: How stable is the West Antarctic Ice Sheet?

Exceeding critical temperature limits in the Southern Ocean may cause the collapse of ice sheets and a sharp rise in sea levels

A future warming of the Southern Ocean caused by rising greenhouse gas concentrations in the atmosphere may severely disrupt the stability of the West...

Im Focus: Superconductivity: footballs with no resistance

Indications of light-induced lossless electricity transmission in fullerenes contribute to the search for superconducting materials for practical applications.

Superconductors have long been confined to niche applications, due to the fact that the highest temperature at which even the best of these materials becomes...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Travel grants available: Meet the world’s most proficient mathematicians and computer scientists

09.02.2016 | Event News

AKL’16: Experience Laser Technology Live in Europe´s Largest Laser Application Center!

02.02.2016 | Event News

From intelligent knee braces to anti-theft backpacks

26.01.2016 | Event News

 
Latest News

About injured hearts that grow back - Heart regeneration mechanism in zebrafish revealed

10.02.2016 | Life Sciences

The most accurate optical single-ion clock worldwide

10.02.2016 | Earth Sciences

Absorbing acoustics with soundless spirals

10.02.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>