Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Designed proteins to treat muscular dystrophy

29.06.2017

The cell scaffolding holds muscle fibers together and protects them from damage. Individuals who suffer from muscular dystrophy often lack essential components in this cell scaffold. As a result, their muscles lack strength and become progressively weaker. The research team of Prof. Markus Rüegg at the Biozentrum, University of Basel, has now designed two proteins that stabilize the cell scaffolding link it to the muscle fiber and thereby restore muscle structure and function. Their findings are published in the current issue of “Science Translational Medicine”.

Muscular dystrophy is a term used to describe many different muscular diseases caused by genetic defects. To date, there are no treatments available to stop disease progression. In their study, the scientists led by Prof. Markus Rüegg have investigated a specific type of muscular dystrophy, called congenital muscular dystrophy.


Querschnitt einer Muskelbiopsie: Blutgefässe (rot) zwischen den Muskelfasern und Laminin-α2 (grün), welches jede Muskelfaser ummantelt.

Universität Basel, Biozentrum

In an animal model, they demonstrated for the first time that two proteins designed by the researchers not only recover muscle force and increase body weight in the sick animals but also significantly prolong survival.

Severe impairments due to congenital muscular dystrophy

Congenital muscular dystrophy is a rare and severe form of a muscular dystrophy that presents at birth or during infancy. “The children born with this disease are also called ′floppy infants′ because of the poor muscle tone and weakness,” says Judith Reinhard, first author of the study.

“The disease becomes more severe with increasing age, as the muscle wasting progresses.” Affected children are often unable to walk independently or they lose this ability with age. The respiratory muscles are also affected. The lifespan is often short and many patients die before reaching adulthood.

Defective gene – defective cell scaffolding

This form of muscular dystrophy results from a genetic defect in laminin-α2. This protein is a key component of the cell scaffolding and connects it with the inner part of the muscle fiber, ensuring the stability of the tissue. Consequently, as a result of gene defects in laminin-α2 the muscles are extremely unstable and even normal use of the muscles leads to muscle injuries, inflammation and finally to the degeneration of muscle fibers. In these diseased muscles, which are unable to produce laminin-α2, another laminin takes over. This protein, called laminin-α4, however, is only a poor replacement because it is not well integrated into the cell scaffolding.

Proteins anchor cell scaffolding and stabilize muscle fibers

The researchers designed two proteins that allow the integration of laminin-α4 and anchor it to the muscle cell. “Using these linkers, we were able to stabilize the muscle fibers,” explains Rüegg. “When animals with a laminin-α2 defect express the two linkers, there was a significant improvement in muscle structure and force and an increase in body weight. We were particularly pleased to observe that these animals also had an almost normal lifespan. Some of them even survived their healthy siblings.” Furthermore, the scientists examined muscle biopsies of patients with congenital muscular dystrophy. They found very similar structural defects and laminin-α4 was also found in place of laminin-α2 in the diseased muscle fibers.

“Both of the designed linker proteins may possibly be used in the future as a gene therapy treatment for congenital muscular dystrophy,” says Rüegg. “Our study is a nice example of how the understanding of a disease on the molecular and cellular level results in new therapeutic options. We are now interested in whether these linker proteins also improve muscle function as well as affect survival in advanced stages of congenital muscular dystrophy.”

Original article

Judith R. Reinhard, Shuo Lin, Karen K. McKee, Sarina Meinen, Stephanie C. Crosson, Maurizio Sury, Samantha Hobbs, Geraldine Maier, Peter D. Yurchenco and Markus A. Rüegg.
Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice.
Science Translational Medicine, published online 28 June 2017

Further information

Markus Rüegg, University of Basel, Biozentrum, Tel. +41 61 207 22 23, email: markus-a.ruegg@unibas.ch

Katrin Bühler | Universität Basel
Further information:
http://www.unibas.ch

Further reports about: dystrophy fibers gene therapy muscle fibers muscular dystrophy

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>