Treatment of Progressive Multifocal Leukoencephalopathy With Interleukin 7

Alstadhaug, Karl Bjørnar; Croughs, Thérèse; Henriksen, Stian; Leboeuf, Céline; Sereti, Irini; Hirsch, Hans H.; Rinaldo, Christine Hanssen

doi:10.1001/jamaneurol.2014.825

Cited by 83 publications

(66 citation statements)

References 15 publications

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“…It is important to note that although this study excluded ICL patients with poorly controlled opportunistic infections because of safety concerns, rhIL-7 has been enlisted for compassionate use in 3 cases of progressive multifocal leukoencephalopathy with apparent success. [49][50][51] In conclusion, the results of this study demonstrate that rhIL-7 is safe and well tolerated in ICL and can induce cycling and expansion of T cells in peripheral blood and tissues in even the most severely lymphopenic patients. The results of this study provide the basis for further evaluation of clinical efficacy of rhIL-7 therapy in treatment of ICL patients.…”

Section: Discussionmentioning

confidence: 56%

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Sheikh

Porter

DerSimonian

et al. 2016

Blood

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Section: Discussionmentioning

confidence: 56%

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Sheikh

Porter

DerSimonian

et al. 2016

Blood

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“…The disease mainly affects individuals afflicted with HIV-AIDS or patients undergoing treatment with certain immunomodulatory monoclonal antibodies, but it can also affect transplant patients and patients with hematological diseases or idiopathic CD4 T-cell lymphocytopenia (3)(4)(5). A few cases of PML in immunocompetent individuals have also been described (6,7).…”

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confidence: 99%

Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells

Sharma

Marschall

Rinaldo

2014

Antimicrob Agents Chemother

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The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosuppression are at risk for infection, and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity in vitro but limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication in vitro. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in the extracellular JCPyV DNA load 96 h postinfection, with a 50% effective concentration (EC 50 ) of 2.9 M. This effect correlated with a decreased expression of capsid protein VP1 and a reduced release of infectious viral progeny. For concentrations of <20 M, transient reductions in cellular DNA replication and proliferation were seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in the mock-infected cells, but interestingly, cellular DNA replication in the JCPyV-infected cells was more strongly affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations, which are achievable in plasma. The inhibition at EC 50 probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results, together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggest a potential use for artesunate in patients with PML.

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“…Had he not contracted community-acquired pneumonia in January 2014, he might have been well at an overall better performance level. We did not find any cause, i.e., no active PML signs for his deterioration after pneumonia, and hence did not treat him with interleukin-7, a promising new agent for PML patients (Alstadhaug et al 2014). His worse performance was mainly due to increased ataxia which might be due to increased brain atrophy at the former midline-lesion site.…”

Section: Discussionmentioning

confidence: 89%

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine

et al. 2015

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Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

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Treatment of Progressive Multifocal Leukoencephalopathy With Interleukin 7

Cited by 83 publications

References 15 publications

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia

Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine

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