RxPG News Feed for RxPG News

Medical Research Health Special Topics World
  Home
 
   Health
 Aging
 Asian Health
 Events
 Fitness
 Food & Nutrition
 Happiness
 Men's Health
 Mental Health
 Occupational Health
 Parenting
 Public Health
 Sleep Hygiene
 Women's Health
 
   Healthcare
 Africa
 Australia
 Canada Healthcare
 China Healthcare
 India Healthcare
 New Zealand
 South Africa
 UK
 USA
 World Healthcare
 
   Latest Research
 Aging
 Alternative Medicine
 Anaethesia
 Biochemistry
 Biotechnology
 Cancer
 Cardiology
 Clinical Trials
 Cytology
 Dental
 Dermatology
 Embryology
 Endocrinology
 ENT
 Environment
 Epidemiology
 Gastroenterology
 Genetics
  Cloning
  Genetic Disorders
   Brachydactyly
   Fragile X Syndrome
   Huntington's
   MSUD
   Progeria
  X Chromosome
 Gynaecology
 Haematology
 Immunology
 Infectious Diseases
 Medicine
 Metabolism
 Microbiology
 Musculoskeletal
 Nephrology
 Neurosciences
 Obstetrics
 Ophthalmology
 Orthopedics
 Paediatrics
 Pathology
 Pharmacology
 Physiology
 Physiotherapy
 Psychiatry
 Radiology
 Rheumatology
 Sports Medicine
 Surgery
 Toxicology
 Urology
 
   Medical News
 Awards & Prizes
 Epidemics
 Launch
 Opinion
 Professionals
 
   Special Topics
 Ethics
 Euthanasia
 Evolution
 Feature
 Odd Medical News
 Climate

Last Updated: Oct 11, 2012 - 10:22:56 PM
Genes & Development Genetic Disorders Channel

subscribe to Genetic Disorders newsletter
Latest Research : Genetics : Genetic Disorders

   EMAIL   |   PRINT
Switching genes to overdrive improves muscular dystrophy symptoms in mice

Apr 1, 2007 - 11:56:50 AM , Reviewed by: Dr. Rashmi Yadav
“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.”

 
[RxPG] 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.



Publication: Genes & Development
On the web: http://www.dfci.harvard.edu/ 

Advertise in this space for $10 per month. Contact us today.


Related Genetic Disorders News
XXYY syndrome- features and treatment options elucidated by researchers
Switching genes to overdrive improves muscular dystrophy symptoms in mice
Gene mutation associated with X-linked mental retardation revealed
Link between Huntington's and abnormal cholesterol levels in brain discovered
Williams Syndrome, the brain and music
Exploring genetics of congenital malformations
FDA Approves Idursulfase As First Treatment for Hunter Syndrome
PARP1 inhibitors can protect Huntington's disease affected cells from damage
Gene therapy protects neurons in Huntington's disease
Huntingtin cleavage is caused by caspase-6

Subscribe to Genetic Disorders Newsletter

Enter your email address:


 About Dr. Rashmi Yadav
This news story has been reviewed by Dr. Rashmi Yadav before its publication on RxPG News website. Dr. Rashmi Yadav, MBBS, is a senior editor for RxPG News. In her position she is responsible for managing special correspondents and the surgery section of the website. Her areas of special interest include cardiothoracic surgery and interventional radiology.
RxPG News is committed to promotion and implementation of Evidence Based Medical Journalism in all channels of mass media including internet.
 Additional information about the news article
Spiegelman said that his team is collaborating with researchers at the Broad Institute of Harvard and MIT in searching through libraries of drugs or drug-like compounds already approved by the Food and Drug Administration that could increase PGC-1alpha levels. Other searches are going on in the biotech and pharmaceutical industry, added Spiegelman.

The studies were supported by grants from the National Institutes of Health.

Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
 Feedback
For any corrections of factual information, to contact the editors or to send any medical news or health news press releases, use feedback form

Top of Page

 
Contact us

RxPG Online

Nerve

 

    Full Text RSS

© All rights reserved by RxPG Medical Solutions Private Limited (India)