Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecular cause of hereditary disease discovered

04.09.2014

The Wiskott-Aldrich syndrome is a rare and severe hereditary disease. A hitherto unsuspected protein is believed to be involved in the development of the disease. The "Nature Communications" journal reports on these new findings from Würzburg.

The disease is characterised by thrombocytopenia and immune deficiency with patients suffering from eczema, increased risk of internal bleeding and permanent infections such as otitis media, pneumonia or meningitis to mention the main symptoms of Wiskott-Aldrich syndrome. The incidence of the rare hereditary disease is only one to four cases in a million births, with boys being affected almost exclusively.


Platelets of healthy persons and mice have a dense cytoskeleton (red) fringed by a ring of microtubules (green). In Wiskott-Aldrich patients and mice with a gene defect at Profilin1, things differ.

Pictures: Simon Stritt

The only cure of the syndrome is a bone marrow transplant. Where that is not possible, the symptoms are treated, among others, with immunoglobulins to compensate for the immune deficiency or by giving platelet transfusions. Low platelet counts are typical of the disease resulting in a blood coagulation disorder.

"The disease is believed to be directly caused by a defect of the Wiskott-Aldrich syndrome protein WASp," says professor Bernhard Nieswandt of the University of Würzburg. However, it has been impossible to prove this assumption in laboratory tests on mice to date. But recently the medical scientist and his team have pinpointed another protein as a potential contributor to the hereditary disease as the Würzburg research team reports in the "Nature Communications" journal.

Defective platelet production

How did the researchers come to this conclusion? Nieswandt and his team are basically interested in platelets and their function in the blood coagulation process. They analysed the role of the protein Profilin1 for the production of platelets from precursor cells in mice and found interesting evidence: "The platelets in mice with a defective Profilin1 gene were reduced in size and number exactly as in Wiskott-Aldrich syndrome," explains doctoral candidate Simon Stritt.

Abnormal cytoskeleton is highly stable

The scientist then discovered even more similarities: The platelets of the mice with the gene defect are smaller than usual, because their cytoskeletal architecture is abnormal while being exceptionally stable. They detected the same mutations in the platelets of four Wiskott-Aldrich patients. "What is more, the Profilin1 in the patients' platelets is found in different places than usual," Stritt further says. This finding also points to the protein being involved in causing Wiskott-Aldrich syndrome.

Significance for treating the syndrome

Direct consequences for treating Wiskott-Aldrich syndrome cannot be derived from this finding. The protein Profilin1 is not a suitable target structure for drugs as it occurs in nearly all cells of the body. "A drug targeting Profilin1 would entail significant side effects," says the doctoral candidate.

However, the Würzburg scientists discovered that clodronate, a drug used to treat osteoporosis, could be beneficial in treating the disease: It raised the platelet count in mice with the gene defect to a normal level. This could be a new starting point to treat thrombocytopenia in Wiskott-Aldrich patients.

Next research steps

"Our goal next is to understand the molecular mechanism by which the proteins Profilin1 and WASp interact and how this results in defects in the platelet production and the organisation of the cytoskeleton," the researchers say. Moreover, they want to find out whether Profilin1 also contributes to the development of the immune deficiency in Wiskott-Aldrich patients.

Bender, M. and Stritt, S. et al.: Megakaryocyte-specific Profilin1-deficiency alters microtubule stability and causes a Wiskott-Aldrich syndrome-like platelet defect. Nature Communications, 5:4746 doi: 10.1038/ncomms5746 (2014, september 4)

Contact

Prof. Dr. Bernhard Nieswandt, Chair of Experimental Biomedicine, University of Würzburg, phone +49 931 31-80406, bernhard.nieswandt@virchow.uni-wuerzburg.de

Robert Emmerich | idw - Informationsdienst Wissenschaft
Further information:
http://www.uni-wuerzburg.de

More articles from Life Sciences:

nachricht Perseus translates proteomics data
27.07.2016 | Max-Planck-Institut für Biochemie

nachricht Severity of enzyme deficiency central to favism
26.07.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-assembling nano inks form conductive and transparent grids during imprint

Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.

To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...

Im Focus: The Glowing Brain

A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology

On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...

Im Focus: Newly discovered material property may lead to high temp superconductivity

Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.

While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

New study reveals where MH370 debris more likely to be found

27.07.2016 | Earth Sciences

Dirty to drinkable

27.07.2016 | Materials Sciences

Exploring one of the largest salt flats in the world

27.07.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>