Low-dose tacrolimus for intractable myasthenia gravis

Yoshikawa, Hiroaki; Mabuchi, Kazunori; Yasukawa, Yoshihiro; Takamori, Masaharu; Yamada, Masahito

doi:10.1054/jocn.2001.0907

Cited by 36 publications

(19 citation statements)

References 12 publications

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“…These findings indicate that nine patients enrolled in this study were steroid-dependent and in these cases, the dose of PSL was successfully reduced by the administration of tacrolimus. A previous study on tacrolimus for the treatment of MG indicated that clinical improvement was achieved so rapidly that muscle strength improved two weeks after the initiation of tacrolimus (Yoshikawa et al, 2002a). In the present study, patients remained in MMS during the observation periods; however, the PSL dose was reduced within six months from the beginning of tacrolimus administration.…”

Section: Discussionmentioning

confidence: 52%

“…Some non-steroidal immunosuppressants can achieve clinical improvements or reduce the side effects of corticosteroids, tacrolimus being one prime example (Evoli et al, 2002;Konishi et al, 2005;Yoshikawa et al, 2002a).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported in non-controlled studies that low-dose administration of tacrolimus is effective and safe in combination with steroids for MG (Evoli et al, 2002;Konishi et al, 2005;Yoshikawa et al, 2002a). A distinguishing feature of tacrolimus is that its effect appears early after its administration.…”

Section: Introductionmentioning

confidence: 99%

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Clinical efficacy and cytokine network-modulating effects of tacrolimus in myasthenia gravis

Furukawa

Yoshikawa

Iwasa

et al. 2008

Journal of Neuroimmunology

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To clarify the long-term efficacy, safety and the cytokine network-modulating effects of tacrolimus in myasthenia gravis, medical records of 86 newly diagnosed consecutive patients and nine steroid-dependent patients were retrospectively reviewed, and peripheral blood mononuclear cells (PBMC) were cultured for the cytokine profile.Steroid reduction effects were observed by using tacrolimus, and no serious adverse effects were observed. The culture study showed reduced IL-12, IL-17, IFN-γ, GM-CSF, TNF-α and MIP-1β, and elevated IL-10 in the PBMC from patients who received tacrolimus, which suggests inhibition of T cells and macrophages, and enhancement of type 1 regulatory T cells.

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Section: Discussionmentioning

confidence: 52%

Section: Discussionmentioning

confidence: 99%

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Clinical efficacy and cytokine network-modulating effects of tacrolimus in myasthenia gravis

Furukawa

Yoshikawa

Iwasa

et al. 2008

Journal of Neuroimmunology

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“…In this study, a significant correlation between the clinical response of MG patients to the therapy assessed by anti-ACh-R Ab levels or total amounts of FK506 administrated and Rh123 efflux activity of PBMCs was not found. However, most of the MG patients treated by FK506 have undergone successful clinical courses, 24,25) and the ACh-R Ab levels or MG scores were improved or preserved in MG patients during the course of FK506 therapy in this study (Fig. 4).…”

Section: Discussionmentioning

confidence: 52%

P-Glycoprotein Function in Peripheral Blood Mononuclear Cells of Myasthenia Gravis Patients Treated with Tacrolimus

Tanaka

Hirano

Saito

et al. 2007

Biological & Pharmaceutical Bulletin

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Myasthenia gravis (MG) is an autoimmune disorder generally mediated by antibodies against the acetylcholine receptors (ACh-R) of skeletal muscles.1) Production of these antibodies in B cells depends upon ACh-R specific T cells.2) In general, four therapeutic strategies are available for MG: enhancement of neuromuscular transmission by means of anticholinesterase agents, thymectomy, immunosuppression with glucocorticoids (GCs) and plasma exchange. 1)In addition to GCs, tacrolimus (FK506) is currently used for the treatment of MG. The drug acts by inhibiting calcium-calcineurin pathways, which results in a reduction of T cell proliferation.3) We have previously reported on the individual variations in the suppressive potencies of FK506 on in vitro blastogenesis of PBMCs from MG patients. 4)The MDR-1 gene codes for a drug efflux pump P-gp, 5) which is expressed on the surface of lymphocytes 6) and actively transports these ligands, including FK506, out of target cells, thereby reducing their efficacy. 7) These substrates for P-gp may induce P-gp overexpression in either PBMCs or select drug-resistant cell subpopulations.MDR-1 gene expression and its corresponding protein membrane density in clinical samples have been studied by quantitation of P-gp mRNA with the reverse transcriptasepolymerase chain reaction (RT-PCR) and by immuno-histochemical techniques.8) However, the evaluation of MDR-1 or P-gp with these methods was not found to be parallel with the data for functional P-gp, 9) ignoring the possibility that regulation may occur at the transcriptional, translational, and/or post-translational levels. An alternative approach, consisting of the measurement of the extrusion of fluorescent dyes from individual cells, was found to allow for the evaluation of the functional activity of P-gp. 10)This study was undertaken to examine the influence of FK506 therapy on P-gp function in PBMCs and the relationship between P-gp function and PBMC-sensitivity to FK506 in vitro. In addition, we will also report on the clinical response to FK506 in MG patients. 11 Bq/mmol) was purchased from New England Nuclear Co., U.S.A. The other reagents were of the best available grade. MATERIALS AND METHODS ReagentsSubjects In this study, 10 MG patients and 18 healthy subjects, as a control, were included. The clinical characteristics of the patients are summarized in Table 1. Six patients received FK506 and four patients were administered prednisolone (PSL) as an immunosuppressant and/or anticholinesterase agents. FK506 was administered at a daily dose of 3 mg. PSL was administered before and during the present study. Most of the patients (8/10) had undergone a thymectomy before immunosuppressive drug administration. Eighteen healthy control subjects (8 male and 10 female; 25.3Ϯ6.2 years of age) were concurrently included in the study. Twenty milliliters of venous blood from each subject were obtained and heparinized. The study using human PBMCs was approved by the ethical committee of Tokyo University of Pharmacy and life Science, and co...

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“…Previous reports showed an early effect of tacrolimus treatment [6,8,[11][12][13][14]. Tacrolimus improved muscle strength at only 2 weeks after the treatment commenced in a 2002 study [11] and other studies also showed significant clinical improvement, for example in lower limb muscle strength [8], MG-ADL, and serum levels of anti-AChR antibodies [14], shortly after patients were started on the drug.…”

Section: Discussionmentioning

confidence: 94%