Featured Research

from universities, journals, and other organizations

Regenerating muscle in Duchenne muscular dystrophy: Age matters

Date:
April 14, 2014
Source:
Sanford-Burnham Medical Research Institute
Summary:
Novel cellular and molecular elements of muscle repair have been revealed by researchers. A new study explains how drugs can induce regeneration, while preventing fibrosis and fat deposition, in dystrophic muscle at early stages of Duchenne muscular dystrophy, an incurable muscle-wasting disease.

HDAC inhibitors (HDACi) promote muscle regeneration in a mouse model of Duchenne Muscular Dystrophy at early stages of disease by targeting fibro-adipogenic progenitors (FAPs). Staining of FAPs from muscles of HDACi-treated young mdx mice reveals presence of differentiated muscle cells (green) at the expense of fat cells (red). Nuclei are stained in blue.
Credit: Lorenzo Puri, M.D.

A team of scientists led by Pier Lorenzo Puri, M.D., associate professor at Sanford-Burnham Medical Research Institute (Sanford-Burnham), in collaboration with Fondazione Santa Lucia in Rome, Italy, have published details of how a class of drugs called "HDACis" drive muscle-cell regeneration in the early stages of dystrophic muscles, but fail to work in late stages. The findings are key to furthering clinical development of HDACis for Duchenne muscular dystrophy (DMD), an incurable muscle-wasting disease.

A symphony to rebuild muscle

The research, to be published April 15 in Genes and Development, used mouse models of DMD to show how fibro-adipogenic progenitor cells (FAPs) act like orchestra conductors in the music of muscle regeneration. FAPs sit in the space between muscle fibers and coordinate a complex symphony -- receiving the notes that muscle has been damaged and directing muscle stem cells -- satellite cells -- to rebuild muscle.

"HDACis create an environment conducive for FAPs to direct muscle regeneration -- but only during the early stages of DMD progression in mice," said Puri. "At some point, DMD progresses to a pathological point of no return and become permanently resistant to muscle-regeneration cures and to HDACis. HDACis open the blueprints for muscle regeneration

HDACis stands for histone deacetylase inhibitors. They are epigenetic drugs that work by facilitating the accessibility to the genes that code for muscle proteins by the cell machinery that transcribes the genetic code into proteins. In essence, HDACis open the blueprints for protein manufacturing and instruct FAPs to support muscle regeneration.

In normal wear and tear, FAPs direct stem cells within the muscle to regenerate and repair damaged muscle. In DMD, the persistent breakdown of muscle cells creates an environment in such disarray that FAP's ability to direct muscle regeneration is compromised -- like trying to conduct a symphony with punk rock music in the background.

Collaborating to find a treatment for DMD

Puri, along with his Italian colleagues at Fondazione Santa Lucia, Italfarmaco, and Parent Project Muscular Dystrophy, an advocacy association, are currently developing HDACis for the treatment of DMD -- a clinical trial with DMD boys is currently ongoing.

"Our study is important because it provides the rational for the clinical development of HDACis to treat DMD," said Puri. "And, now that we understand the mechanics and sensitivities of the muscle-regeneration system, we have the rationale and can use new tools to select patients most likely to benefit from HDACIs based on their FAP profile, predict outcomes, and see how long patients should remain on the therapy."

"Duchenne muscular dystrophy patients and their families rely on important research such as that performed by Dr. Puri," said Debra Miller, Founder of Cure Duchenne, a patient advocacy group. "Our efforts at Cure Duchenne are to support leading scientists in the world to bring life-saving drugs to help this generation of Duchenne boys, and our vision is to cure Duchenne muscular dystrophy. Every added piece of knowledge about the disease brings us closer to realizing our goals."


Story Source:

The above story is based on materials provided by Sanford-Burnham Medical Research Institute. Note: Materials may be edited for content and length.


Journal Reference:

  1. V. Saccone, S. Consalvi, L. Giordani, C. Mozzetta, I. Barozzi, M. Sandona, T. Ryan, A. Rojas-Munoz, L. Madaro, P. Fasanaro, G. Borsellino, M. De Bardi, G. Frige, A. Termanini, X. Sun, J. Rossant, B. G. Bruneau, M. Mercola, S. Minucci, P. L. Puri. HDAC-regulated myomiRs control BAF60 variant exchange and direct the functional phenotype of fibro-adipogenic progenitors in dystrophic muscles. Genes & Development, 2014; DOI: 10.1101/gad.234468.113

Cite This Page:

Sanford-Burnham Medical Research Institute. "Regenerating muscle in Duchenne muscular dystrophy: Age matters." ScienceDaily. ScienceDaily, 14 April 2014. <www.sciencedaily.com/releases/2014/04/140414091747.htm>.
Sanford-Burnham Medical Research Institute. (2014, April 14). Regenerating muscle in Duchenne muscular dystrophy: Age matters. ScienceDaily. Retrieved October 20, 2014 from www.sciencedaily.com/releases/2014/04/140414091747.htm
Sanford-Burnham Medical Research Institute. "Regenerating muscle in Duchenne muscular dystrophy: Age matters." ScienceDaily. www.sciencedaily.com/releases/2014/04/140414091747.htm (accessed October 20, 2014).

Share This



More Health & Medicine News

Monday, October 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Microneedle Patch Promises Painless Pricks

Microneedle Patch Promises Painless Pricks

Reuters - Innovations Video Online (Oct. 18, 2014) Researchers at The National University of Singapore have invented a new microneedle patch that could offer a faster and less painful delivery of drugs such as insulin and painkillers. Video provided by Reuters
Powered by NewsLook.com
Raw: Nurse Nina Pham Arrives in Maryland

Raw: Nurse Nina Pham Arrives in Maryland

AP (Oct. 17, 2014) The first nurse to be diagnosed with Ebola at a Dallas hospital walked down the stairs of an executive jet into an ambulance at an airport in Frederick, Maryland, on Thursday. Pham will be treated at the National Institutes of Health. (Oct. 16) Video provided by AP
Powered by NewsLook.com
Raw: Cruise Ship Returns to US Over Ebola Fears

Raw: Cruise Ship Returns to US Over Ebola Fears

AP (Oct. 17, 2014) A Caribbean cruise ship carrying a Dallas health care worker who is being monitored for signs of the Ebola virus is heading back to Texas, US, after being refused permission to dock in Cozumel, Mexico. (Oct. 17) Video provided by AP
Powered by NewsLook.com
Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

Spanish Govt: Four Suspected Ebola Cases in Spain Test Negative

AFP (Oct. 17, 2014) All four suspected Ebola cases admitted to hospitals in Spain on Thursday have tested negative for the deadly virus in a first round of tests, the government said Friday. Duration: 00:55 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins