443extremely severe courses of the disease. The high therapeutic effi cacy of this
substance, which originates from oncology, is coupled with potential, in part dose-
dependent side effects on the heart, reproductive organs, and the bone marrow; thus
the pros and cons of its administration must be weighted. Predictors of therapeutic
response may result in individualized risk stratifi cation and MX dosing.
It is known that diverse immune cells respond differently to mitoxantrone lead-
ing to the hypothesis that specifi c drug carriers – proteins that eliminate mitoxan-
trone from the cells – have different infl uences on different cells as well as on the
effectiveness of the drug in different patients. ATP-binding cassette-transporters
ABCB1 and ABCG2 represent multi-drug resistance mechanisms involved in active
cellular MX effl ux. The role of ABC-gene SNPs for clinical MX response has been
investigated in multiple sclerosis patients in Germany, corroborated by experimen-
tal in vitro and in vivo data (Cotte et al. 2009 ). 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. The investiga-
tors were able to prove that the genetic blueprint of specifi c transporter proteins
allows one to draw conclusions on the effectiveness and risk of side effects of the
potent agent mitoxantrone and they hope to be able to develop personalized treat-
ment plans for each patient.
Personalized Cell Therapy of Multiple Sclerosis
Autologous Bone Marrow Stem Cell Therapy for Multiple Sclerosis
Bone marrow stem cells have been shown in several experimental studies to have
benefi cial effects in disease models of MS. Safety and feasibility of intravenous,
autologous bone marrow cell therapy, without immunosuppressive preconditioning,
was tested in a phase I study in six patients with clinically defi nite, relapsing-
progressive multiple sclerosis (Rice et al. 2010 ). Assessment of effi cacy was a sec-
ondary objective and employed clinical disability rating scales, multimodal evoked
potential (MMEP) recordings, and MRI scans. Cells were harvested, fi ltered and
infused intravenously in a day-case procedure that was well tolerated by patients
and was not associated with any serious adverse events. Over a period of 1 year
after the therapy, clinical disability scores showed either no change or improve-
ment, and MMEPs showed neurophysiological improvement. MRI scans did not
show any signifi cant changes over a post-therapy period of 3 months. The lack of
serious adverse effects and the suggestion of a benefi cial effect in this small sample
of patients with progressive disease justify conducting a larger phase II/III study to
make a fuller assessment of the effi cacy of mobilization of autologous bone marrow
stem cells in patients with MS.
Personalized Treatment of Multiple Sclerosis