Navigation Links
Switching Genes to Overdrive Improves Muscular Dystrophy Symptoms in Mice

BOSTON -- Scientists at Dana-Farber Cancer Institute have shown in a laboratory study that revving up a crucial set of muscle genes counteracts// the damage caused by a form of muscular dystrophy.

Reporting in the April 1 issue of Genes and Development, the researchers demonstrated that manipulating a genetic molecular switch increased the genes’ activity in the muscles of mice with Duchenne muscular dystrophy, slowing the disease-associated muscle wasting. The authors caution that they have not yet found a way to tweak the switch, known as PGC-1alpha, in humans.

“I think that if we could elevate the levels of PGC-1alpha in the muscles of patients with Duchenne muscular dystrophy, it is likely that we could slow or reduce the course of the disease,” said Bruce Spiegelman, PhD, the Dana-Farber researcher who led the team along with Christoph Handschin, PhD, formerly of Dana-Farber and now at the University of Zurich. Other authors are from the University of Iowa College of Medicine.

Duchenne muscular dystrophy (DMD) is the most common type of muscular dystrophy in children, occurring once in about every 5,000 live births of boys, and is ultimately fatal. The average age of death is the mid-teens, and most patients die by their 30s. In the United States, about 400 to 600 boys are born each year with DMD or Becker Muscular Dystrophy, a milder form of the disease. The cause is a mutation, either inherited or occurring spontaneously, that affects a muscle protein called dystrophin.

Spiegelman, whose laboratory discovered PGC-1alpha in 1998, led the new study which was aimed at determining whether increasing levels of PGC-1alpha in the muscles of mice could increase the activity of genes that are known to behave abnormally in muscular dystrophy.

PGC-1alpha is known as a “transcriptional coactivator” that functions as a switch, or perhaps more accurately, like a light dimmer that increases or decreases the activit y of genes under its control. Exercising a muscle raises PGC-1alpha levels, causing the formation of more mitochondria, the chemical power plants that create energy in cells.

PGC-1alpha is also required for the normal operation of genes that control the development of neuromuscular junctions (NMJ) – sites on muscle fibers where nerves attach and signal the fibers to contract. Part of the reason that exercise builds stronger muscles is that it increases PGC-1alpha activity. Conversely, disease or lack of exercise reduces PGC-1alpha activity, causing a loss of NMJ function and weakening, or atrophying, of muscles.

Spiegelman’s team had previously bred a strain of mice with higher-than-normal levels of PGC-1alpha in their muscles. Also available for the research was a mouse model of Duchenne muscular dystrophy, the MDX mouse. In the new experiment, the scientists bred male high-PGC-1alpha mice with female MDX mice (the muscular dystrophy gene is carried by females in mouse and in humans.) As a result, the offspring of these matings had muscular dystrophy but also had elevated PGC-1alpha. Using exercise and chemical tests, the researchers compared muscle function in the offspring with MDX mice having no additional PGC-1alpha.

Both sets of rodents were run on a treadmill for one hour, then again 24 hours later. Normal mice completed the runs easily on both days, while untreated MDX rodents were exhausted halfway through each run. The MDX mice with increased PGC-1alpha activity performed almost as well as normal mice on the first day; their performances decreased on the second day, but they still did better than the untreated MDX mice on both runs.

The exercise tests and microscopic and chemical examinations of the muscles showed that boosting PGC-1alpha caused “a clear and substantial improvement in the structure and function of skeletal muscle in this disease model,” the scientists wrote.

Source-Eurekaler
SR M
'"/>




Related medicine news :

1. Switching drugs regularly improves HIV treatment
2. Switching Off Protein Could Play Key Role In Success Of Radiation Therapy For Cancer
3. New Way to "See" Genes, Evaluate Effectiveness of Gene Therapies Discovered
4. Genes for lung disease
5. Genesis of SUPAC
6. Genes for Vision discovered
7. Genes Found To Help Leukemia Treatment
8. Cardiac Valve Disease Linked To Genes
9. Genes Linked To Cigarette Addiction
10. Genes from saliva may predict oral and breast cancer
11. Genes More Important Than Exercise for Bad Cholesterol
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/2/2016)... , ... May 02, 2016 , ... The 2016 World Ultimate & Guts Championship (WUGC) ... at Manhattan College, made the cut. The WUGC is being held in London, England this ... the gold in the men’s division, another gold in the women’s masters division, and a ...
(Date:5/2/2016)... ... , ... Pregnancy Awareness Month offers a great time to get familiar with ... are ready to have a baby, it’s best to get started before age becomes ... Personal Conception & Pregnancy Organizer, written for women who plan on becoming pregnant to ...
(Date:5/2/2016)... ... May 02, 2016 , ... A ... completed two groundbreaking studies that determined that the adjustability and adaptability of pediatric ... the prevention of pressure injuries, which are now referred to as “pressure injuries” ...
(Date:5/2/2016)... ... May 02, 2016 , ... Atlantic Information Services, Inc. (AIS) ... B Payment Model Could Transform the Pharma Landscape .” CMS recently proposed a test ... spend on provider-administered drugs while preserving care provided to beneficiaries. The webinar will review ...
(Date:5/2/2016)... ... May 02, 2016 , ... The Evolve Paddle Board Company- ... prices announced today the outcome of their partnership with Yoloha Yoga- producers of high ... Yoga Board.” , SUP yoga has seen a dramatic rise in popularity throughout the ...
Breaking Medicine News(10 mins):
(Date:4/29/2016)... PUNE, India , April 29, 2016 /PRNewswire/ ... - Pipeline Review, H1 2016" market research report ... pipeline, complete with comparative analysis at various stages, ... (MoA), route of administration (RoA) and molecule type, ... press releases. It also reviews key players involved ...
(Date:4/29/2016)... Glycotope GmbH, a clinical-stage immuno-oncology company built ... Dr. Alfredo Zurlo as Chief Medical Officer. ... years clinical experience and a proven track record in ... at Mologen AG where he was Chief Medical Officer ... held various positions at F Hoffmann La Roche and ...
(Date:4/28/2016)... NEW YORK , April 28, 2016 /PRNewswire/ ... will notably complement the company,s valve repair and ... the move also places Abbott more firmly into ... one of the fastest growing device areas, with ... to its recent report,  Advanced Remote Patient ...
Breaking Medicine Technology: