Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Osteoporosis: Antibody crystallised

05.09.2016

Inhibiting a protein called Sclerostin could probably help treating the bone-loss disease osteoporosis. New findings at the University of Würzburg could stimulate this research.

Osteoporosis particularly affects elderly women: the bone’s structure weakens and the risk of suffering fractures rises. As prophylaxis patients are advised to have a healthy diet and perform physical exercises; when the risk of bone fractures is high, medicine preventing further bone loss is prescribed in addition.


Model of a Sclerostin-fragment (green) bound to the antibody AbD09097 (heavy and light chain in cyan and red, respectively; surface representation in grey)

(Figure: Thomas Müller)

In the search for better treatments for this disease the protein Sclerostin, which plays an important role in bone metabolism, is of major interest. When its function is impeded, bone resorption diminishes and bone re-growth is stimulated.

First clinical trials with a Sclerostin-inhibiting antibody developed by the companies Amgen and UCB showed promising results in that the bone mass of participants suffering from osteoporosis increased. Currently, studies are continued at several locations, amongst others Würzburg, Munich and Dresden.

Verena Boschert, Postdoc in the team of structural biologist Prof. Thomas Müller at the Julius-von-Sachs Institute (Julius-Maximilians-Universität Würzburg, JMU, in Bavaria, Germany) is also working on the protein Sclerostin. In a collaborative project with several project partners and funded by the European Union and the Deutsche Forschungsgemeinschaft novel Sclerostin-inhibiting antibodies were generated and analysed for their suitability as osteoporosis treatment option.

Now, for the first time the JMU scientists crystallized an antibody effective against Sclerostin and analysed its mode of action in detail. Recently, these results were published in the journal Open Biology. “Our findings could have a positive impact on the design of new inhibitory antibodies targeting Sclerostin”, says Boschert.

Cooperation with two companies

In this project the scientists from Würzburg are working together with partners from industry. In cooperation with AbD-Serotec, having its German subsidiary in Puchheim, ten promising antibodies were developed in the initial round. After testing in cell culture one (AbD09097) showed the favoured activity to neutralize Sclerostin.

Together with the company Pepscan (Lelystad/ The Netherlands) and the Leibniz Institute for Pharmacology in Berlin an in-depth analysis of the binding epitopes was performed using peptide chemistry and NMR spectroscopy. From these methods the binding site of the antibody in Sclerostin could be deduced.

Further steps in the project

”Until now, we could only determine the structure of the antibody alone “, Boschert points out. As the next step it is planned to crystallize the antibody together with Sclerostin or a binding fragment. Thereby, a more detailed view of the interaction between antibody and its target will be obtained.

The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6. V. Boschert, C. Frisch, J. W. Back, K. van Pee, S. E. Weidauer, E.-M. Muth, P. Schmieder, M. Beerbaum, A. Knappik, P. Timmerman, T. D. Mueller. Open Biology 2016 6 160120; DOI: 10.1098/rsob.160120. Published 24 August 2016

Contact

Prof. Dr. Thomas Müller, Biocenter, Julius-von-Sachs Institute, JMU, T +49 31 31-89207, mueller@biozentrum.uni-wuerzburg.de

Dr. Verena Boschert, Biocenter, Julius-von-Sachs Institute, JMU, T +49 931 31-80910, verena.boschert@uni-wuerzburg.de

Weitere Informationen:

http://rsob.royalsocietypublishing.org/content/6/8/160120 Link to Open-Access article

Robert Emmerich | Julius-Maximilians-Universität Würzburg

More articles from Life Sciences:

nachricht When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short
23.03.2017 | Institut für Pflanzenbiochemie

nachricht WPI team grows heart tissue on spinach leaves
23.03.2017 | Worcester Polytechnic Institute

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

When Air is in Short Supply - Shedding light on plant stress reactions when oxygen runs short

23.03.2017 | Life Sciences

Researchers use light to remotely control curvature of plastics

23.03.2017 | Power and Electrical Engineering

Sea ice extent sinks to record lows at both poles

23.03.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>