Navigation Links
Switching genes to overdrive improves muscular dystrophy symptoms in mice

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 activity 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:Dana-Farber Cancer Institute


Related biology news :

1. Switching to new anti-bacterial targets: Riboswitches
2. Newly-discovered class of genes determines ?and restricts ?stem cell fate
3. Inexpensive, mass-produced genes core of synthetic biology advances at UH
4. First atlas of key brain genes could speed research on cancer, neurological diseases
5. U-M scientists find genes that control growth of common skin cancer
6. Researchers find missing genes of ancient organism
7. Scientists document complex genomic events leading to the birth of new genes
8. Genrate: a generative model that finds and scores new genes and exons in genomic microarray data
9. Advances in the characterisation of the oyster mushroom genes
10. Researchers find new genes necessary to make embryo
11. Protein helps regulate the genes of embryonic stem cells

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/2/2016)... -- The Department of Transport Management (DOTM) of ... US Dollar project, for the , Supply and ... and IT Infrastructure , to Decatur ... of Identity Management Solutions. Numerous renowned international vendors participated in ... was selected for the most compliant and innovative solution. ...
(Date:6/2/2016)... 2016 Perimeter Surveillance & Detection ... Physical Infrastructure, Support & Other Service  The ... offers comprehensive analysis of the global Border Security ... revenues of $17.98 billion in 2016. Now: ... leader in software and hardware technologies for advanced video ...
(Date:5/24/2016)... , May 24, 2016 Ampronix facilitates superior patient care by providing ...  3D medical LCD display is the latest premium product recently added to the range ... ... ... Sony 3d Imaging- LCD Medical Display- Ampronix News ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016 /PRNewswire/ - FACIT has announced the ... biotechnology company, Propellon Therapeutics Inc. ("Propellon" or ... of a portfolio of first-in-class WDR5 inhibitors for ... as WDR5 represent an exciting class of therapies, ... medicine for cancer patients. Substantial advances have been ...
(Date:6/23/2016)... MA (PRWEB) , ... June 23, 2016 , ... ... Peel Plate® YM (Yeast and Mold) microbial test has received AOAC Research Institute ... platform of microbial tests introduced last year,” stated Bob Salter, Vice President of ...
(Date:6/23/2016)... 23, 2016   EpiBiome , a precision microbiome ... in debt financing from Silicon Valley Bank (SVB). The ... to advance its drug development efforts, as well as ... "SVB has been an incredible strategic partner to ... traditional bank would provide," said Dr. Aeron Tynes ...
(Date:6/23/2016)... ... 23, 2016 , ... In a new case report published today in STEM ... who developed lymphedema after being treated for breast cancer benefitted from an injection of ... dealing with this debilitating, frequent side effect of cancer treatment. , Lymphedema ...
Breaking Biology Technology: