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 Aromatic couple makes new chemical bonds
30.06.2015 | Institute of Transformative Bio-Molecules (ITbM), Nagoya University

nachricht Breaking through a double wall with a sledgehammer
29.06.2015 | Max-Planck-Institut für Entwicklungsbiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Iron: A biological element?

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and a half billion years ago.

Think of an object made of iron: An I-beam, a car frame, a nail. Now imagine that half of the iron in that object owes its existence to bacteria living two and...

Im Focus: Thousands of Droplets for Diagnostics

Researchers develop new method enabling DNA molecules to be counted in just 30 minutes

A team of scientists including PhD student Friedrich Schuler from the Laboratory of MEMS Applications at the Department of Microsystems Engineering (IMTEK) of...

Im Focus: Bionic eye clinical trial results show long-term safety, efficacy vision-restoring implant

Patients using Argus II experienced significant improvement in visual function and quality of life

The three-year clinical trial results of the retinal implant popularly known as the "bionic eye," have proven the long-term efficacy, safety and reliability of...

Im Focus: Lasers for Fast Internet in Space – Space Technology from Aachen

On June 23, the second Sentinel mission was launched from the space mission launch center in Kourou. A critical component of Aachen is on board. Researchers at the Fraunhofer Institute for Laser Technology ILT and Tesat-Spacecom have jointly developed the know-how for space-qualified laser components. For the Sentinel mission the diode laser pump module of the Laser Communication Terminal LCT was planned and constructed in Aachen in cooperation with the manufacturer of the LCT, Tesat-Spacecom, and the Ferdinand Braun Institute.

After eight years of preparation, in the early morning of June 23 the time had come: in Kourou in French Guiana, the European Space Agency launched the...

Im Focus: Superslippery islands (but then they get stuck)

A simple reversible process that changes friction in the nanoworld

(Nano)islands that slide freely on a sea of copper, but when they become too large (and too dense) they end up getting stuck: that nicely sums up the system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

World Conference on Regenerative Medicine: Abstract Submission has been extended to 24 June

16.06.2015 | Event News

MUSE hosting Europe’s largest science communication conference

11.06.2015 | Event News

 
Latest News

Aromatic couple makes new chemical bonds

30.06.2015 | Life Sciences

Extreme makeover: Mankind's unprecedented transformation of Earth

30.06.2015 | Earth Sciences

Large-scale field-effect transistors based on solution-grown organic single crystals are fabricated

30.06.2015 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>