Featured Research

from universities, journals, and other organizations

Tamoxifen ameliorates symptoms of Duchenne muscular dystrophy, study suggests

Date:
January 15, 2013
Source:
Elsevier
Summary:
A new study has found that tamoxifen, a well-known breast cancer drug, can counteract some pathological features in a mouse model of Duchenne muscular dystrophy (DMD). At present, no treatment is known to produce long-term improvement of the symptoms in boys with DMD, a debilitating muscular disorder that is characterized by progressive muscle wasting, respiratory and cardiac impairments, paralysis, and premature death.

The mice were allowed to grasp a metal wire maintained horizontally above a thick layer of soft bedding (upper left). After exploring the wire for a short period of time (upper right), the mice tried to pull themselves on the wire (bottom left), a very energy-demanding exercise, until they lost grip of their hind paws and hung onto the wire with their forelimbs only (bottom right). From this position, the untreated mdx5Cv mice were unable to sustain their own body weight for more than a few seconds before falling, whereas the mdx5Cv mice treated with tamoxifen (not shown) performed much better and as well as normal mice.
Credit: Dorchies et al.

A new study has found that tamoxifen, a well-known breast cancer drug, can counteract some pathological features in a mouse model of Duchenne muscular dystrophy (DMD). At present, no treatment is known to produce long-term improvement of the symptoms in boys with DMD, a debilitating muscular disorder that is characterized by progressive muscle wasting, respiratory and cardiac impairments, paralysis, and premature death.

This study will be published in the February 2013 issue of The American Journal of Pathology.

Using the mdx5Cv mouse model of DMD, investigators found that tamoxifen, given orally for more than a year, "caused remarkable improvements of muscle force and of diaphragm and cardiac structure," according to lead author Olivier M. Dorchies, PhD, of the Department of Pharmacology, Geneva-Lausanne School of Pharmaceutical Sciences of the University of Geneva and University of Lausanne. For instance, in the heart, fibrosis was diminished by approximately 50%. In the diaphragm, the muscle of the dystrophic mouse thought to be most like that of human DMD, tamoxifen reduced fibrosis while increasing thickness as well as the number and average diameter of muscle fibers. The net effect was that tamoxifen raised the amount of contractile tissue available for respiration by 72%.

Patients with DMD show muscle degeneration, and their muscle fibers become abnormally susceptible to stress. In this animal study, tamoxifen improved the structure of leg muscles, slowed muscle contraction, increased overall muscle function, and made leg muscles more resistant to repetitive stimulation and fatigue. In fact, tamoxifen rendered dystrophic muscles even stronger than those of non-dystrophic control mice. "Our findings of a slower rate of contraction and an enhanced resistance to fatigue in muscles from tamoxifen-treated dystrophic mice are of significance for the pathophysiology of muscular dystrophy," say the authors.

A wire test revealed that treating male mdx5Cv mice with tamoxifen for more than a year increased the whole body strength 2- to 3-fold, close to that of normal mice.

Additional findings shed light on the mechanism of tamoxifen's therapeutic actions. For example, plasma creatine kinase (CK) activity was found to be about 3 times higher in the dystrophic male mice than in the non-dystrophic males, and tamoxifen treatment normalized the CK levels of the dystrophic mice. The authors suggest that this effect is mediated by an estrogen receptor (ER) dependent mechanism. The study also reported for the first time that mouse dystrophic muscle is high in both ER α and β, and that tamoxifen raises levels of ERβ2 in particular. Other findings, such as increased levels of calcineurin and accumulation of several structural proteins, indicate a protective effect of tamoxifen on dystrophic muscles. The authors point out that the beneficial effects of tamoxifen were seen with muscle tissue levels much lower than those reported in previous studies of normal rodents, suggesting that doses lower than those used to treat breast cancer may be effective in the treatment of DMD.


Story Source:

The above story is based on materials provided by Elsevier. Note: Materials may be edited for content and length.


Journal Reference:

  1. Olivier M. Dorchies, Julie Reutenauer-Patte, Elyes Dahmane, et al. The anti-cancer drug tamoxifen counteracts the pathology in a mouse model of Duchenne muscular dystrophy. The American Journal of Pathology, Volume 182, Issue 2 (February 2013) DOI: 10.1016/j.ajpath.2012.10.018

Cite This Page:

Elsevier. "Tamoxifen ameliorates symptoms of Duchenne muscular dystrophy, study suggests." ScienceDaily. ScienceDaily, 15 January 2013. <www.sciencedaily.com/releases/2013/01/130115085843.htm>.
Elsevier. (2013, January 15). Tamoxifen ameliorates symptoms of Duchenne muscular dystrophy, study suggests. ScienceDaily. Retrieved September 22, 2014 from www.sciencedaily.com/releases/2013/01/130115085843.htm
Elsevier. "Tamoxifen ameliorates symptoms of Duchenne muscular dystrophy, study suggests." ScienceDaily. www.sciencedaily.com/releases/2013/01/130115085843.htm (accessed September 22, 2014).

Share This



More Health & Medicine News

Monday, September 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Sierra Leone in Lockdown to Control Ebola

Sierra Leone in Lockdown to Control Ebola

AP (Sep. 21, 2014) Sierra Leone residents remained in lockdown on Saturday as part of a massive effort to confine millions of people to their homes in a bid to stem the biggest Ebola outbreak in history. (Sept. 20) Video provided by AP
Powered by NewsLook.com
Sierra Leone's Nationwide Ebola Curfew Underway

Sierra Leone's Nationwide Ebola Curfew Underway

Newsy (Sep. 20, 2014) Sierra Leone is locked down as aid workers and volunteers look for new cases of Ebola. Video provided by Newsy
Powered by NewsLook.com
Changes Found In Brain After One Dose Of Antidepressants

Changes Found In Brain After One Dose Of Antidepressants

Newsy (Sep. 19, 2014) A study suggest antidepressants can kick in much sooner than previously thought. Video provided by Newsy
Powered by NewsLook.com
Could Grief Affect The Immune Systems Of Senior Citizens?

Could Grief Affect The Immune Systems Of Senior Citizens?

Newsy (Sep. 19, 2014) The study found elderly people are much more likely to become susceptible to infection than younger adults going though a similar situation. Video provided by Newsy
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:
from the past week

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