Suppression of demyelination by mitoxantrone

Watson, C. M.; Davison, Alan; Baker, David; O'Neill, J.K.; Turk, J.L.

doi:10.1016/0192-0561(91)90045-9

Cited by 55 publications

(35 citation statements)

References 20 publications

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“…), preceding the onset of clinical signs on days 15-19 p.i., which generally progress to complete hind limb paralysis. The animals then enter a period of clinieal remission and spontaneously exhibit further paralytic relapse episodes [2][3][4][5]. This CREAE model provides a means for examining potential therapeutic agents and strategies for the control of an ongoing immune response in the CNS.…”

Section: Introductionmentioning

confidence: 99%

“…doses of 2 5 mg/kg MX could completely inhibit the development of acute phase CREAE when treated from day 12 p.i. onwards and relapsing CREAE when Biozzi AB/H mice were treated during the post-acute remission period [4]. Although many immunosuppressive compounds can prevent the majority of animals developing EAE when treated from day 9 p.i.…”

Section: Introductionmentioning

confidence: 99%

“…MX is a potent immunosuppressive agent which inhibits an in vivo induced proliferative response in a dose-dependent manner [4]. Repeated systemic doses of 1 mg/kg failed to inhibit the oxazolone-induced proliferation and also the development of EAE when AB/H mice were treated from day 12 p.i.…”

Section: Introductionmentioning

confidence: 99%

“…Repeated systemic doses of 1 mg/kg failed to inhibit the oxazolone-induced proliferation and also the development of EAE when AB/H mice were treated from day 12 p.i. onwards [4] . However, it has been shown that repeated i.p.…”

Section: Introductionmentioning

confidence: 99%

“…This may be studied in the T cell-mediated, demyelinating disease, chronic relapsing experimental allergic encephalomyelitis (CREAE) [I]. Recently it has been shown that following immunization with syngeneic spinal cord homogenate (SCH) in Freund's adjuvant, an inbred strain of Biozzi AB/H mice exhibit a highly reproducible and predictable form of CREAE, where the majority ofthe pathology that accompanies clinical CREAE occurs in the spinal cord [2][3][4][5][6]. Disease is characterized in the initial, acute phase by preclinical weight loss on days 13-15 post-inoculation (p.i.…”

Section: Introductionmentioning

confidence: 99%

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Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone

Baker

O'Neill

Davison

et al. 1992

Clinical and Experimental Immunology

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SUMMARY Mitoxantrone was used as an immunosuppressive probe to elucidate a means for the control of experimental allergic enccphalomyelitis (EAE) induced in Biozzi AB/H mice following injection of spinal cord homogenate emulsified in Freund's adjuvant. A single i.p. injection of 2–5 mg/kg of mitoxantrone, 1–2 days before the anticipated onset of EAE, failed to prevent the majority of animals from developing clinical disease, whereas when the compound was injected directly into the central nervous system (CNS), at this time point, significantly increased therapeutic benefit was evident, with most animals failing to develop clinical EAE. Although the clinical use of intrathecal mitoxantrone is strongly contraindicated, these data suggest that increased therapeutic benefit may be achieved in immune‐mediated disease of the CNS by targeting immunosuppressive doses of suitable agents, on lymphocyte activation within the CNS. In addition, direct administration of immunosuppressive doses into the CNS may reduce potentially unwanted (side) effects in the periphery.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone

Baker

O'Neill

Davison

et al. 1992

Clinical and Experimental Immunology

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Inhibition by Mitoxantrone of In Vitro Migration of Immunocompetent Cells

Kopadze¹,

Dehmel²,

Hartung³

et al. 2006

Arch Neurol

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Background: Damage of the blood-brain barrier and invasion of immunocompetent cells into the central nervous system represent key events in the immunopathogenesis of multiple sclerosis. Mitoxantrone hydrochloride reduces progression of disability and clinical exacerbations in patients with multiple sclerosis. Its precise mode of action is unclear. Objective: To investigate the effects of mitoxantrone on the migratory capacity of immunocompetent cells ex vivo and in vitro.

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Efficacy and Safety of Mitoxantrone in Patients With Highly Relapsing Neuromyelitis Optica

Kim

Kim²,

Park³

et al. 2011

Arch Neurol

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To evaluate the efficacy and safety of mitoxantrone hydrochloride and determine how it exhibits a differential inhibitory effect on subsets of B cells in patients with highly relapsing neuromyelitis optica (NMO). Design: Retrospective case series with prospective follow-up. Setting: Three referral medical centers in the Republic of Korea. Patients: Twenty patients with highly relapsing NMO or neuromyelitis optica spectrum disorder who had at least 2 relapses during the year preceding the start of mitoxantrone treatment, despite other immunotherapies. Intervention: Infusions of mitoxantrone up to a maximum cumulative dose of 120 mg/m 2. Main Outcome Measures: Annualized relapse rate, disability according to the Expanded Disability Status Scale score, and fraction of CD27 ϩ CD19 ϩ memory B cells. Results: During mitoxantrone treatment, the median annualized relapse rate was reduced by 75%, and 50% of patients became relapse free. Disability improved or stabilized in all patients. No patients had serious adverse effects during the mean follow-up period of 41 months after completing therapy. Flow cytometric analysis of cell surface markers revealed that mitoxantrone treatment preferentially affected CD27 ϩ CD19 ϩ memory B cells. Conclusions: Treatment with mitoxantrone in patients with highly relapsing NMO significantly reduces relapse rates, resulting in subsequent functional stabilization or improvement.

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Suppression of demyelination by mitoxantrone

Cited by 55 publications

References 20 publications

Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone

Control of immune-mediated disease of the central nervous system requires the use of a neuroactive agent: elucidation by the action of mitoxantrone

Inhibition by Mitoxantrone of In Vitro Migration of Immunocompetent Cells

Efficacy and Safety of Mitoxantrone in Patients With Highly Relapsing Neuromyelitis Optica

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