Pixantrone (BBR2778): a new immunosuppressant in multiple sclerosis with a low cardiotoxicity

@article{Gonsette2004PixantroneA,
  title={Pixantrone (BBR2778): a new immunosuppressant in multiple sclerosis with a low cardiotoxicity},
  author={Richard E Gonsette},
  journal={Journal of the Neurological Sciences},
  year={2004},
  volume={223},
  pages={81-86}
}
  • R. Gonsette
  • Published 15 August 2004
  • Medicine, Biology
  • Journal of the Neurological Sciences

Pixantrone (BBR2778) Reduces the Severity of Experimental Autoimmune Myasthenia Gravis in Lewis Rats1

TLDR
The effectiveness and the reduced cardiotoxicity make PIX a promising immunosuppressant agent suitable for clinical investigation in MG, although additional experiments are needed to confirm its safety profile in prolonged treatments.

Compared benefit of approved and experimental immunosuppressive therapeutic approaches in multiple sclerosis

  • R. Gonsette
  • Biology, Medicine
    Expert opinion on pharmacotherapy
  • 2007
TLDR
Recent observations strongly suggest that early administration of potent immunosuppressants (mitoxantrone and alemtuzumab) is definitely more effective than approved immunomodulators to delay or even reverse disability progression.

Immunosuppressive agents in multiple sclerosis

Mitoxantrone for multiple sclerosis.

TLDR
MX shows a significant but partial efficacy in reducing the risk of MS progression and the frequency of relapses in patients affected by worsening RRMS, PRMS and SPMS in the short-term follow-up (two years) and should be considered with caution.

Therapeutic Effect of Anthracene-Based Anticancer Agent Ethonafide in an Animal Model of Multiple Sclerosis1

TLDR
It is demonstrated that ethonafide is effective in preventing development of EAE as well as in ameliorating the severity of E AE when disease is ongoing, and evidences are provided that eth onafide has less cardiac toxicity compared with MIT.

Review of Novel Immunotherapeutic Strategies for MS

TLDR
This chapter provides a compilation of novel immunotherapeutic strategies or new aspects of known immunotherAPEutic agents that have evolved in recent years and their immunopathogenetic rationale as well as the accompanying preclinical and clinical data to support their potential to endorse the currently available disease modifying drugs.

Disease Modifying Agents in the Treatment of Multiple Sclerosis

TLDR
All currently approved disease-modifying agents (DMA) are moderately effective in reducing relapses and MRI activity and the effect on long-term disability seems to be modest if any.

Immunosuppression in clinical practice

TLDR
Practical aspects in the clinical use of immunosuppressants in MS are reviewed and approaches to individualized treatment schemes, including novel pharmacogenetic strategies are discussed.

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Mitoxantrone immunotherapy in multiple sclerosis

TLDR
Mitoxantrone, when employed properly, may be useful in patients with frequent and disabling excerbations and/or rapidly progressing disability, and that the benefit is limited to the period of administration of any treatment.

Die immunsuppressive Therapie der multiplen Sklerose mit Mitoxantron

TLDR
Preliminary clinical results indicate that the cytostatic agent mitoxantrone is an effective and very tolerable substance for treating multiple sclerosis and therefore its use should be restricted to patients with rapid disease progression where other generally accepted treatment modalities have failed.

Mitoxantrone in progressive multiple sclerosis: when and how to treat?

  • R. Gonsette
  • Medicine, Biology
    Journal of the Neurological Sciences
  • 2003

Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS

TLDR
Records of 1,378 patients from three clinical trials of MITO treatment for MS were reviewed for signs and symptoms of cardiac dysfunction and left ventricular ejection fraction (LVEF) results and the observed incidence of CHF in patients with MS was <0.20%.

A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis

TLDR
The observed incidence proportion of t-AL is very low in patients who received MITO as single-agent therapy for MS, and extended follow-up of these patients and those who receive higher cumulative doses of MITO is required to define the long-term risk.

Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function.

TLDR
Flow cytometric analysis revealed a dramatic decrease in splenic B lymphocyte content, and mitoxantrone exerted a potent suppressive influence on the humoral immune system through a direct reduction in B cell number augmented by macrophage-mediated inhibition of B cell proliferation.

Suppression of demyelination by mitoxantrone.

Bbr 2778, an Aza-anthracenedione Endowed with Preclinical Anticancer Activity and Lack of Delayed Cardiotoxicity

TLDR
Although against in vivo models BBR 2778 was less potent than mitoxantrone and doxorubicin, its antitumor activity was equal or superior (in certain tumor models) to that of the above standard compounds.

Protective effects of erdosteine against doxorubicin‐induced cardiomyopathy in rats

TLDR
It was concluded that erdosteine caused an increase in the activities of antioxidant enzymes, especially GSH‐Px and CAT, protecting the heart tissue sufficiently from oxidative damage to membrane lipids and other cellular components induced by DXR.