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:8/17/2017)... ... August 17, 2017 , ... SeQuel Response announced today ... growth agency among the fastest-growing private companies in the U.S., putting it in the ... that have applied to the Inc. 5000 over the years, only a ...
(Date:8/17/2017)... Tree, CO (PRWEB) , ... August 17, 2017 , ... ... called Exilis in Lone Tree, CO, at Atagi Plastic Surgery and Skin Aesthetics. ... using a potent combination of radiofrequency and ultrasound energy. Smoother, younger-looking skin is revealed ...
(Date:8/17/2017)... ... August 17, 2017 , ... An August 2 article on ... plastic surgery, largely influenced by the growing popularity of “pretty boys” in both K-Pop ... that standards of male appearance are changing not only in the Asian nation, where ...
(Date:8/17/2017)... ... August 17, 2017 , ... With the introduction of new devices, new features, ... changes to the smartwatch market. As of June 2017, nearly nine percent of U.S. ... months prior. Additionally, according to latest WEAR Report Industry Overview and Forecast from NPD’s ...
(Date:8/17/2017)... CO (PRWEB) , ... August 17, 2017 , ... ... Moral Injury: The Journey to Healing Through Forgiveness ($15.99, paperback, 9781498497626; $7.99, ... (war) trauma, to encourage inner healing of memories and achieve forgiveness, through a ...
Breaking Medicine News(10 mins):
(Date:8/17/2017)... CAESAREA, Israel , August 17, 2017 /PRNewswire/ ... digital health Company with mobile health and big ... securities purchase agreements with domestic and non-U.S. investors ... common stock and shares of the Company,s newly ... private placement offerings. The Company expects to conduct ...
(Date:8/17/2017)... Aug. 17, 2017 Bio-Ess Laboratories, LLC Chief Science Officer, Dr. ... and present new data on Cell-Ess® Universal Titer Boost at ... Boston, MA August 21-25.  The Bioprocessing Summit convenes more than ... ... ...
(Date:8/15/2017)... , Aug. 15, 2017   Mostyn Law and Gulf ... Houston, Texas . The Mostyn Law family ... 2 years. That is why Mostyn Law is partnering ... to show its appreciation. Blood supplies are running ... 5% short of hospital needs in August. That is why the ...
Breaking Medicine Technology: