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.


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:

(Date:11/30/2015)... ... November 30, 2015 , ... RoamRight, a leading provider ... with Public Television’s Travel With Kids to promote family vacations around the ... as they explore international destinations and educate families about the people and places of ...
(Date:11/30/2015)... ... November 30, 2015 , ... Advocare Orthopedic ... orthopedic care. Led by John Vitolo, M.D., the center offers their patients ... team at Advocare Orthopedic & Sports Medicine is ready to help their patients ...
(Date:11/30/2015)... Pittsburgh, PA (PRWEB) , ... November 30, 2015 ... ... according to a new study by UPMC and KingMed Diagnostics ... UPMC over three years found that consultation with UPMC pathologists resulted in significantly ...
(Date:11/30/2015)... ... ... The American Society for Clinical Pathology (ASCP) announced today that it has ... 30, ASCP shared its “Give a minute. Get tested. Find a cure.” icon and ... getting tested for HIV. , ASCP has asked members to replace their Facebook, Twitter, ...
(Date:11/30/2015)... ... November 30, 2015 , ... An inventor from Charlottesville, ... the womb. "My last baby had high blood pressure due to loud noises," she ... protect their babies from noise pollution as well as radio waves and microwaves." , ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... BOSTON , Nov. 30, 2015  Kevin ... of Sensium Healthcare, a global pioneer in wireless ... Boston, MA , Mr. Smith ... of Sensium,s global commercial strategy.  He will also ... universities, to build clinical evidence for SensiumVitals, the ...
(Date:11/30/2015)... , Nov. 30, 2015  The fee-for-service ... in U.S. medical imaging is on its ... accountable care payer-provider contracts are set to ... their wake, alter provider-vendor relationships. The shift ... push forward new purchasing frameworks in the ...
(Date:11/30/2015)... WOODCLIFF LAKE, N.J. and SAN ... Inc. and Arena Pharmaceuticals, Inc. (NASDAQ: ARNA ) ... (FDA) has accepted for filing the New Drug Application ... approved, the extended release formulation will offer patients a ... ® ) is currently approved as ...
Breaking Medicine Technology: