Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hopes for "tailor-made" MS treatment with Mitoxantrone

31.08.2009
Genetic information may enable personalized treatment schedule
Results obtained by neurologists in Bochum lead to BMBF-subsidized study

In view of the potential severe side effects of new immune therapies for multiple sclerosis (MS), research is now focused on the optimized use of established drugs with known side effect profiles. Neurologists in Bochum, working under the auspices of Associate Prof. Andrew Chan (RUB Clinic for Neurology, St. Josef Hospital, Director: Prof. Ralf Gold) are pursuing a pharmacogenetic approach.

They were able to prove that the genetic blueprint of specific transporter proteins allows one to draw conclusions on the effectiveness and risk of side effects of the potent agent mitoxantrone. They hope to be able to develop personalized treatment plans for each individual patient. The results of this study have been published in BRAIN.

Mitoxantrone: highly efficient escalation therapy in multiple sclerosis

According to data supplied by the German Multiple Sclerosis Society's national MS register (DMSG - Deutsche Multiple Sklerose Gesellschaft), up to 10% of German MS patients have been treated with mitoxantrone in the past few years. Numerous studies have shown that it is highly efficient in suppressing disease activity. It is administered as so-called escalation therapy when other medication no longer suffices and in extremely severe courses of the disease. The high therapeutic efficacy of this substance, which originates from oncology, is coupled with potential, in part dose-dependent side effects on the heart, reproductive organs but also on the bone marrow, thus the pros and cons of its administration must be weighted. Prof. Gold stated that, for this very reason, a lifetime maximum dose of mitoxantrone of 140 mg per m2 body surface may not be exceeded.

Signs of the involvement of drug carriers in the effectiveness

Former studies carried out by Dr. Chan and Prof. Gold and their research team had already shown that diverse immune cells respond differently to mitoxantrone. This led to the hypothesis that specific drug carriers - proteins that eliminate mitoxantrone from the cells - have different influences on different cells as well as on the effectiveness of the drug in different patients. The so-called ATP-binding cassette transporters = ABC transporters, thus became the most interesting aspect. The researchers assumed that less potent transporters are accompanied by a higher mitoxantrone concentration within the cells and thus higher effectiveness, and vice versa, that highly functional transporters reduce the effectiveness of the drug.

Genetic blueprint of the transporter influences the effectiveness

They went on to test this hypothesis on a group of MS patients from all over Europe (cooperation with clinics in Dresden, Berg, Göttingen, and Barcelona). It was shown that the differing genetic blueprints of ABC-transporters are indeed linked to the therapeutic response to mitoxantrone. The probability of the patient group with a genetic disposition to low transporter activity responding positively to mitoxantrone is 3,5 times higher than in the group with genetically caused higher transporter activity. Moreover, the functional effects of these genotypes were also confirmed in cell culture experiments and in the MS animal model. Dr. Chan pointed out that the first data gained is also indicative of a correlation between the genetic blueprint of the transporter protein and the side effects of mitoxantrone, for example in isolated cases with cardiac side effects.

Extensive study in the competence network MS should confirm results

Dr. Chan explained, "These results furnish hope for personalized mitoxantrone therapy schedules, for example with adapted single doses. This could also result in longer-term total therapy times being possible, a factor which is particularly important because corresponding follow-up therapy periods have not yet been clearly established." The results of the retrospective study must however first be confirmed in a prospective manner on a large group of patients. The corresponding study within the frameworks of the nation-wide competence network MS, which is subsidized by the Federal Ministry of Education and Research (BMBF - Bundesforschungsministerium), will moreover also investigate further potential pharmacogenetic markers in correlation with mitoxantrone treatment. Prof. Gold and Dr. Chan explained that their primary target is the establishment of a personalized MS treatment strategy for every patient taking the individual aspects of the patient into consideration. These investigations may make it possible to incorporate individual genetic patterns in the decision on the therapy.

Title

Cotte S, von Ahsen N, Kruse N, Huber B, Winkelmann A, Zettl UK, Starck M, König N, Tellez N, Dörr J, Paul F, Zipp F, Lühder F, Koepsell H, Pannek H, Montalban X, Gold R, Chan A: ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis. In: Brain, epub ahead of print, Jul 15, doi:10.1093/brain/awp164

Further Information

Associate Professor Dr. Andrew Chan, Neurological Clinic at the Ruhr-University Bochum in St. Josef Hospital, Gudrunstraße 56, 44791 Bochum, Tel.: 0234/509-2411, Fax: 0234/509-2414, E-Mail: Andrew.Chan@rub.de

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de/

More articles from Studies and Analyses:

nachricht Innovative genetic tests for children with developmental disorders and epilepsy
11.07.2018 | Christian-Albrechts-Universität zu Kiel

nachricht Oxygen loss in the coastal Baltic Sea is “unprecedentedly severe”
05.07.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Future electronic components to be printed like newspapers

A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.

The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

A smart safe rechargeable zinc ion battery based on sol-gel transition electrolytes

20.07.2018 | Power and Electrical Engineering

Reversing cause and effect is no trouble for quantum computers

20.07.2018 | Information Technology

Princeton-UPenn research team finds physics treasure hidden in a wallpaper pattern

20.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>