Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New approach to tackle inherited nervous disease

30.09.2015

Scientists from the University of Würzburg have discovered a promising approach to treat a genetically caused nervous disease. Instead of resorting to gene therapy, the scientists have targeted phagocytes they identified as promoters of the disease.

Charcot-Marie-Tooth (CMT) disease is a group of inherited disorders of the peripheral nervous system characterised by loss of nerve fibres, muscle tissue and impaired touch sensation. Early symptoms include paralysis and loss of muscle tissue in the feet and legs expanding to the hands and lower arms as the disease progresses. In severe cases, sufferers need a wheelchair; and there is no efficient therapy available at present.

Publication in the journal Brain

This could change in the foreseeable future: Scientists at the Department of Neurology of the University Hospital of Würzburg have found a target for therapy that was successfully applied in animal tests. The team of Professor Rudolf Martini, head of Experimental Developmental Neurobiology at the Department of Neurology has now published these findings in the renowned journal Brain.

"Normally, one would expect a gene therapy approach when treating an inherited disease," Martini explains. But he and his team took a different direction: They blocked a receptor on the surface of special cells of the immune system, the so-called macrophages.

A semiochemical gives the cue to attack

In previous studies conducted over several years, the scientists had used model mice to demonstrate that these macrophages cause the genetically predisposed nerve damage to occur in the first place. "You could say that they act as a promoter of the disease," Martini further. A special semiochemical, the cytokine colony-stimulating factor (CSF) -1, signals the macrophages to attack the nerve fibres.

"Astonishingly, CSF-1 is not expressed by the mutated Schwann cells, but by hitherto neglected nerve fibroblasts," Martini says. Schwann cells form the myelin sheaths in the peripheral nervous system which act as a kind of insulation of the myelinated nerve fibres. Moreover, they are essential for the survival of the nerve fibres and thus for keeping the nerves functional.

Even though around 80 disease genes have been identified for CMT neuropathies so far, the three most common forms of this disorder are caused by mutations of myelin associated genes of the Schwann cells. How the fibroblasts are informed about the defective Schwann cells is still unknown, but the scientists hope to decipher the mechanism during further studies.

Visible successes without side effects

In the study, the scientists fed a synthetic CSF-1 receptor inhibitor to mice suffering from CMT. As a result, the symptoms of two different forms of CMT were alleviated significantly and without side effects. The muscular strength experiments were particularly impressive and relevant for patients: "While untreated model mice lost up to 25 percent of their muscular strength due to the disease, the treated mutants cannot be distinguished from their healthy counterparts in terms of muscular strength," Martini says.

Hopes for a quick transfer to clinical practice

The scientists now believe that this approach is also highly significant for the treatment of humans. "Similar inhibitors are already being used in clinical studies to treat rheumatoid arthritis and different tumours," Martini explains. Protracted approval procedures to use the inhibitor on humans are thus already under way.

Dr. Brian West is one of the co-authors of the study besides the members of Martini's team. He is the research director of the Californian company Plexxikon which developed the inhibitor. The study has already drawn much attention, for example, in the form of a scientific comment by Professor Steven S. Scherer (Philadelphia), an international expert in CMT. In addition to Deutsche Forschungsgemeinschaft, the project received considerable funding from Charcot-Marie-Tooth Association in the US, which recently appointed Professor Rudolf Martini to its scientific advisory board.

According to Martini, the successful research project demonstrates that after exploring all other possibilities animal experiments are crucial to finding new approaches to treat and ultimately heal so far incurable human diseases.

Targeting the colony stimulating factor 1 receptor alleviates two forms of Charcot–Marie–Tooth disease in mice. Dennis Klein, Ágnes Patzkó , David Schreiber, Anemoon van Hauwermeiren, Michaela Baier, Janos Groh, Brian L. West and Rudolf Martini. BRAIN, published online August 21, 2015. doi:10.1093/brain/awv240

Contact

Prof. Dr. Rudolf Martini, Phone: +49 931 201-23268, rudolf.martini@mail.uni-wuerzburg.de

Gunnar Bartsch | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-wuerzburg.de

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>