Study of Mitoxantrone for the Treatment of Recurrent Neuromyelitis Optica (Devic Disease)
Harvard University, Cambridge, Massachusetts, United States JAMA Neurology
(Impact Factor: 7.42).
08/2006; 63(7):957-63. DOI: 10.1001/archneur.63.7.957
Neuromyelitis optica is a severe demyelinating disease that selectively involves the optic nerves and the spinal cord but usually spares the brain. It is considered to have a B-cell-induced pathogenesis. Mitoxantrone hydrochloride, a synthetic anthracenedione approved for worsening relapsing-remitting multiple sclerosis and secondary progressive multiple sclerosis, has been shown to primarily suppress the humoral response.
To evaluate the benefit of mitoxantrone treatment in patients with relapsing neuromyelitis optica.
Prospective 2-year study.
Academic multiple sclerosis center.
Five patients (3 women and 2 men) with an age range of 20 to 51 years and an Expanded Disability Status Scale score of 2.5 to 6.5 (mean +/- SD, 4.40 +/- 1.88).
Monthly intravenous infusions of mitoxantrone hydrochloride, 12 mg/m2, for 6 months followed by 3 additional treatments every 3 months.
Expanded Disability Status Scale score measured every 3 months and during relapses; findings on orbital, brain, and spinal cord magnetic resonance images performed at baseline and at 3, 6, 12, 18, and 24 months; and visual evoked potentials and results of ophthalmologic evaluations performed at baseline and annually.
During the 2 years of treatment, 2 patients each had a relapse once within the initial 5 months of treatment (1 severe and 1 moderate). Improvement was seen clinically and on magnetic resonance images in 4 patients. Patients generally tolerated the treatment well, although 1 patient had a reversible decrease in cardiac ejection fraction.
Our results suggest a beneficial effect of mitoxantrone treatment for relapsing neuromyelitis optica.
Available from: Bharath Wootla
- "Interestingly, PLEX proved to be a highly successful treatment for NMO arguing in favor of an immune-mediated pathogenesis of this disease . In line with the autoimmune-mediated hypothesis, humoral immunity-suppressing drugs such as mitoxantrone hydrochloride  (a synthetic anthracenedione that was approved for the treatment of worsening relapsing-remitting and secondary progressive MS), mycophenolate mofetil  (an immunosuppressive therapy), and rituximab  (a B-cell depleting therapy) were demonstrated to be beneficial for treatment of NMO. De Parratt and Prineas recently described an abrupt destruction of perivascular astrocytes in patients with NMO that preceded oligodendrocyte apoptosis in early lesions. "
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ABSTRACT: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS.
05/2012; 2012(1):969657. DOI:10.1155/2012/969657
Available from: Jiwon Oh
- "The efficacy of MITO in NMO was demonstrated in a prospective open-label two-year study where 4 out of 5 patients (80%) showed significant clinical and radiographic improvement. In this study, MITO was generally well tolerated, with one patient having evidence of sub-clinical cardiac insufficiency that recovered after medication discontinuation . A subsequent retrospective case series by Kim et al. showed that MITO resulted in a significant decrease in relapse rate and stabilization or improvement in measures of disability in all patients. "
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ABSTRACT: Neuromyelitis optica (NMO) is a recurrent inflammatory disease that preferentially targets the optic nerves and spinal cord leading to blindness and paralysis. The hallmarks of NMO include bilateral optic neuritis and longitudinally extensive transverse myelitis. Woman and African Americans are overrepresented in the US patient population. NMO is associated with the NMO-IgG biomarker, which targets the aquaporin-4 water channel on astrocytes. The humoral pathology of NMO lesions include IgG and IgM deposits and infiltration by granulocytes suggesting that the NMO-IgG may be involved in the pathogenesis of disease. This review of the recent NMO literature covers the clinical features, epidemiology, radiology and pathology of disease and includes discussion of the important basic science research work in the field.
Neurology Research International 01/2012; 2012(2420):460825. DOI:10.1155/2012/460825
Available from: Jeffrey Lawrence Winters
- "Interestingly, PLEX is a highly successful treatment for NMO arguing in favor of an autoimmune-mediated pathogenesis of this disease. In line with the autoimmune-mediated hypothesis, humoral immunity-suppressing drugs such as Mitoxantrone hydrochloride , (a synthetic anthracenedione that was approved for the treatment of worsening relapsing-remitting and secondary progressive MS), Mycophenolate Mofetil , (an immunosuppressive therapy), and Rituximab , (a B cell depleting therapy) were demonstrated to be beneficial for treatment of NMO. "
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ABSTRACT: The pathogenesis of multiple sclerosis (MS) remains elusive. Recent reports advocate greater involvement of B cells and immunoglobulins in the initiation and propagation of MS lesions at different stages of their ontogeny. The key role of B cells and immunoglobulins in pathogenesis was initially identified by studies in which patients whose fulminant attacks of demyelination did not respond to steroids experienced remarkable functional improvement following plasma exchange. The positive response to Rituximab in Phase II clinical trials of relapsing-remitting MS confirms the role of B cells. The critical question is how B cells contribute to MS. In this paper, we discuss both the deleterious and the beneficial roles of B cells and immunoglobulins in MS lesions. We provide alternative hypotheses to explain both damaging and protective antibody responses.
Neurology Research International 09/2011; 2011:780712. DOI:10.1155/2011/780712
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