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 Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

nachricht Scientists reveal source of human heartbeat in 3-D
07.08.2017 | University of Manchester

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: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New bioimaging technique is fast and economical

21.08.2017 | Medical Engineering

Silk could improve sensitivity, flexibility of wearable body sensors

21.08.2017 | Materials Sciences

On the way to developing a new active ingredient against chronic infections

21.08.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>