Features | Partner Sites | Information | LinkXpress
Sign In
PZ HTL SA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Rapamycin Nanoparticles Correct Autophagy Defects in Mouse Muscular Dystrophy Model

By BiotechDaily International staff writers
Posted on 25 Feb 2014
Image: The mouse in the upper right is the mutant mdx/mdx and is shown with a normal control (Photo courtesy of the Jackson Laboratory).
Image: The mouse in the upper right is the mutant mdx/mdx and is shown with a normal control (Photo courtesy of the Jackson Laboratory).
Nanoparticles coated with rapamycin were found to improve strength and heart function in a mouse model for Duchenne muscular dystrophy.

Duchenne muscular dystrophy in boys progresses rapidly to severe impairment of muscle function and death in the second or third decade of life. Current supportive therapy with corticosteroids results in a modest increase in strength as a consequence of a general reduction in inflammation, but with potential untoward long-term side effects and ultimate failure of the agent to maintain strength.

The primary molecular factor responsible for Duchenne muscular dystrophy is a mutation that prevents the body from producing dystrophin, a protein crucial for maintaining muscle cell integrity and function. In addition, studies with the mdx mouse model of Duchenne muscular dystrophy have shown that defective autophagy is involved in the pathology of the disease.

Investigators at Washington University School of Medicine (St. Louis, MO, USA) looked for ways to correct the autophagy defects. To this end, they developed a class of perfluorocarbon nanoparticles coated with the drug rapamycin. Rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. The drug prevents activation of T-cells and B-cells by inhibiting their response to interleukin-2 (IL-2). It is also used as a coronary stent coating. Rapamycin works, in part, by eliminating old and abnormal white blood cells and is effective in mice with autoimmunity and in children with the rare condition autoimmune lymphoproliferative syndrome (ALPS).

The investigators reported in the February 5, 2014, online edition of the FASEB Journal that following injection, the nanoparticles collected at sites of inflammation, allowing the drug to penetrate muscle tissue. Treated mice showed a 30% increase in grip strength and a significant improvement in cardiac function, based on an increase in the volume of blood the heart pumped. This increase in physical performance occurred in both young and adult mdx mice, and even in aged wild-type mice, which sets the stage for consideration of systemic therapies to facilitate improved cell function by autophagic disposal of toxic byproducts of cell death and regeneration.

“Autophagy plays a major role in disposing of cellular debris,” said senior author Dr. Samuel A. Wickline, professor of medicine at Washington University School of Medicine. “If it does not happen, you might say the cell chokes on its own refuse. In muscular dystrophy, defective autophagy is not necessarily a primary source of muscle weakness, but it clearly becomes a problem over time. If you solve that, you can help the situation by maintaining more normal cellular function.”

“An important aspect of our study is that we are treating both skeletal muscle and heart muscle with the same drug,” said Dr. Wickline. “The heart is a difficult organ to treat in muscular dystrophy. But even in older animals, this regimen works well to recover heart function, and it is effective over a short period of time and after only a few doses.”

Related Links:

Washington University School of Medicine



BIOSIGMA S.R.L.
RANDOX LABORATORIES
SLAS - Society for Laboratory Automation and Screening
comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: The Human Protein Atlas is tissue-based map of the human proteome (Photo courtesy of the Human Protein Atlas).

Open Source Tissue-Based Map of the Human Proteome Launched

Constructed with 13 million annotated images, an interactive database has been created to show the distribution of proteins in all major tissues and organs of the human body. Ten years after the completion... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Lab Technologies

view channel

e-Incubator Technology Provides Real-Time Imaging of Bioengineered Tissues in a Controlled Unit

A new e-incubator, an innovative miniature incubator that is compatible with magnetic resonance imaging (MRI), enables scientists to grow tissue-engineered constructs under a controlled setting and to study their growth and development in real time without risk of contamination or damage. Offering the potential to test... Read more

Business

view channel

Two Industry Partnerships Initiated to Fuel Neuroscience Research

Faster, more complex neural research is now attainable by combining technology from two research companies. Blackrock Microsystems, LLC (Salt Lake City, UT, USA), a developer of neuroscience research equipment, announced partnerships with two neuroscience research firms—PhenoSys, GmbH (Berlin, Germany) and NAN Instruments, Ltd.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.