home   genetic news   bioinformatics   biotechnology   literature   journals   ethics   positions   events   sitemap
 
  HUM-MOLGEN -> Genetic News | search  
 

Gene therapy reaches muscles throughout the body and reverses muscular dystrophy in animal mode

 
  August, 3 2004 8:29
your information resource in human molecular genetics
 
     
Researchers have found a delivery method for gene therapy that reaches all the voluntary muscles of a mouse -- including heart, diaphragm and all limbs -- and reverses the process of muscle-wasting found in muscular dystrophy.

"We have a clear 'proof of principle' that it is possible to deliver new genes body-wide to all the striated muscles of an adult animal. Finding a delivery method for the whole body has been a major obstacle limiting the development of gene therapy for the muscular dystrophies. Our new work identifies for the first time a method where a new dystrophin gene can be delivered, using a safe and simple method, to all of the affected muscles of a mouse with muscular dystrophy," said Dr. Jeffrey S. Chamberlain, professor of neurology and director of the Muscular Dystrophy Cooperative Research Center at the University of Washington School of Medicine in Seattle. He also has joint appointments in the departments of medicine and biochemistry.

Chamberlain is the senior author of the paper describing the results, which will be published in the August edition of Nature Medicine. The paper describes a type of viral vector, a specific type of an adeno-associated virus (AAV), which is able to 'home-in' on muscle cells and does not trigger an immune system response. The delivery system also includes use of a growth factor, VEGF, that appears to increase penetration into muscles of the gene therapy agent. Chamberlain said the formula was the result of about a year of trying different methods.

Duchenne muscular dystrophy is an X-linked genetic disorder that strikes one of every 3,500 newborn boys. The genetic disorder eliminates production of the dystrophin protein, which is necessary for the structural support of muscle. Without this protein, muscles weaken to the point where the victim cannot survive.

"By giving one single injection of this AAV vector carrying a mini-dystrophin gene into the bloodstream, we are able to deliver therapeutic levels of dystrophin to every skeletal and cardiac muscle of an adult, dystrophic mouse," Chamberlain said. "These muscles include the heart, the muscles used during breathing, and all the limb muscles. The mice show a whole body effect, with a dramatic improvement of their dystrophy."

The findings hint that it may be possible someday to introduce other genes into adult muscle to address conditions besides muscular dystrophy. The gene therapy developed at the UW was able to perform in all muscles in the mouse, and would not necessarily have to carry the dystrophy gene. Muscle represents about 40 percent of the human body, and there are a number of ailments that involve muscle. Gene therapy could someday reinforce muscles weakened by cancer or normal aging, or treat cardiac disease. But Chamberlain stressed that the paper represents one discovery on the long path to any clinical applications in people.

The results involved mice, so researchers do not know if the method will work in larger animals or people. Chamberlain and colleagues in the Muscular Dystrophy Cooperative Research Center are gathering data to seek regulatory approval for a limited trial in humans to determine the safety of a very small amount of the vector in human muscle. If the experiments take place -- and if results are encouraging -- researchers would continue to test the method in larger animals and hopefully eventually humans. But Chamberlain stressed that there are a number of scientific challenges and regulatory requirements along the way, so any tests on humans are many years in the future.

The research was funded by grants from the National Institutes of Health, the Muscular Dystrophy Association, and Bruce and Jolene McCaw.

Other authors of the paper, all at UW, include co-first authors Drs. Paul Gregorevic and Michael Blankenship, Department of Neurology; James M. Allen, Robert W. Crawford, and Leonard Meuse, also of Neurology; and Daniel G. Miller, Department of Medicine, as well as David W. Russell of the Departments of Medicine and Biochemistry, who identified the particular adeno-associated virus, AAV6, used in the experiments.

© 2004 University of Washington Office of News and Information

Gregorevic P, Blankinship MJ, Allen JM, Crawford RW, Meuse L, Miller DG, Russell DW, Chamberlain JS.
Systemic delivery of genes to striated muscles using adeno-associated viral vectors.
Nat Med. 2004 Aug;10(8):828-34. Epub 2004 Jul 25.


Message posted by: Frank S. Zollmann

print this article mail this article
Bookmark and Share this page (what is this?)

Social bookmarking allows users to save and categorise a personal collection of bookmarks and share them with others. This is different to using your own browser bookmarks which are available using the menus within your web browser.

Use the links below to share this article on the social bookmarking site of your choice.

Read more about social bookmarking at Wikipedia - Social Bookmarking

Latest News
Variants Associated with Pediatric Allergic Disorder

Mutations in PHF6 Found in T-Cell Leukemia

Genetic Risk Variant for Urinary Bladder Cancer

Antibody Has Therapeutic Effect on Mice with ALS

Regulating P53 Activity in Cancer Cells

Anti-RNA Therapy Counters Breast Cancer Spread

Mitochondrial DNA Diversity

The Power of RNA Sequencing

‘Pro-Ageing' Therapy for Cancer?

Niche Genetics Influence Leukaemia

Molecular Biology: Clinical Promise for RNA Interference

Chemoprevention Cocktail for Colon Cancer

more news ...

Generated by News Editor 2.0 by Kai Garlipp
WWW: Kai Garlipp, Frank S. Zollmann.
7.0 © 1995-2016 HUM-MOLGEN. All rights reserved. Liability, Copyright and Imprint.