Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Hopes for "tailor-made" MS treatment with Mitoxantrone

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.


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:

Dr. Josef König | idw
Further information:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

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: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>