A new study has found that tamoxifen, a well-known breast cancer drug, can counteract some pathologic 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 á and â, and that tamoxifen raises levels of ERâ2 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.
David Sampson | EurekAlert!
Study tracks inner workings of the brain with new biosensor
16.08.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
Foods of the future
15.08.2018 | Georg-August-Universität Göttingen
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur
What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...
08.08.2018 | Event News
27.07.2018 | Event News
25.07.2018 | Event News
16.08.2018 | Life Sciences
16.08.2018 | Earth Sciences
16.08.2018 | Life Sciences