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.
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)
Prof. Dr. Bernhard Nieswandt, Chair of Experimental Biomedicine, University of Würzburg, phone +49 931 31-80406, email@example.com
Robert Emmerich | idw - Informationsdienst Wissenschaft
High-arctic butterflies shrink with rising temperatures
07.10.2015 | Aarhus University
Long-term contraception in a single shot
07.10.2015 | California Institute of Technology
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...
At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...
In cooperation with the Center for Nano-Optics of Georgia State University in Atlanta (USA), scientists of the Laboratory for Attosecond Physics of the Max Planck Institute of Quantum Optics and the Ludwig-Maximilians-Universität have made simulations of the processes that happen when a layer of carbon atoms is irradiated with strong laser light.
Electrons hit by strong laser pulses change their location on ultrashort timescales, i.e. within a couple of attoseconds (1 as = 10 to the minus 18 sec). In...
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
08.10.2015 | Earth Sciences
08.10.2015 | Information Technology
08.10.2015 | Physics and Astronomy