JAK 1/2 Blockade in MDA5 Gain-of-Function

McLellan, Kirsty; Martin, Neil; Davidson, Joyce; Cordeiro, N.J.V.; Oates, Bridget D; Neven, Bénédicte; Rice, Gillian I.; Crow, Yanick J.

doi:10.1007/s10875-018-0563-2

Cited by 23 publications

(19 citation statements)

References 7 publications

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“…23,24 Other family members are currently undergoing genetic screening, and treatment with oral Janus kinase 1 and 2 inhibition is currently being considered. 25,26…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

et al. 2019

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IMPORTANCE Neuroinflammatory disorders are a range of severe neurological disorders causing brain and spinal inflammation and are now increasingly recognized in the pediatric population. They are often characterized by marked genotypic and phenotypic heterogeneity, complicating diagnostic work in clinical practice and molecular diagnosis. OBJECTIVE To develop and evaluate a next-generation sequencing panel targeting genes causing neuroinflammation or mimicking neuroinflammation. DESIGN, SETTING, AND PARTICIPANTS Cohort study in which a total of 257 genes associated with monogenic neuroinflammation and/or cerebral vasculopathy, including monogenic noninflammatory diseases mimicking these entities, were selected. A customized enrichment capture array, the neuroinflammation gene panel (NIP), was created. Targeted high-coverage sequencing was applied to DNA samples taken from eligible patients referred to Great Ormond Street Hospital in London,

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“…23,24 Other family members are currently undergoing genetic screening, and treatment with oral Janus kinase 1 and 2 inhibition is currently being considered. 25,26…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

et al. 2019

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“…There are cases of NMO induced by the therapeutic use of recombinant IFN-α for other diseases (10,11). Moreover, there was a case of anti-AQP4-positive NMO in a child with increased endogenous IFN-α level (12). Taken together, elevation of IFN-α in the presence of anti-MDA5 antibody might also affect the pathogenesis or high disease activity of NMO in this study.…”

Section: Discussionmentioning

confidence: 50%

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report

et al. 2020

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Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody is a myositis-specific marker detected in clinically amyopathic dermatomyositis (DM). DM with anti-MDA5 antibody can be accompanied by rapidly progressive interstitial lung disease (RP-ILD) and other autoimmune disorders. Until now, only one case of neuromyelitis optica (NMO) with anti-MDA5-positive DM has been reported worldwide, in which the patient achieved a favorable outcome with intensive immunotherapy. We report a case of NMO in a patient with anti-MDA5-positive DM complicated by ILD and rheumatoid arthritis. Our patient experienced a fulminant course of NMO, rather than RP-ILD, in the presence of hyperferritinemia, which resulted in profound neurological sequelae despite immunotherapy including rituximab.

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“…Of note, a handful of recent reports suggest encouraging results with the use of Janus kinase (JAK) inhibition in several distinct type I interferonopathies, with JAK1 comprising an essential component of the type I interferon receptor complex. We have seen definite improvement in TREX1‐related skin disease and IFIH1‐determined systemic inflammation with the JAK1/2 inhibitor, ruxolitinib. We also described a child with a gain‐of‐function mutation in IFIH1 , apparently demonstrating significant developmental gains, against a background of previous regression and then stagnation, with ruxolitinib therapy .…”

Section: Implications For Therapies Derived From Insights Into Pathogmentioning

confidence: 81%

Treatments in Aicardi–Goutières syndrome

Crow

Shetty

Livingston

2019

Develop Med Child Neuro

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AGSAicardi-Gouti eres syndrome RTI Reverse transcriptase inhibitor Comprehensive reviews of the clinical characteristics and pathogenesis of Aicardi-Gouti eres syndrome (AGS), particularly its contextualization within a putative type I interferonopathy framework, already exist. However, recent reports of attempts at treatment suggest that an assessment of the field from a therapeutic perspective is warranted at this time. Here, we briefly summarize the neurological phenotypes associated with mutations in the seven genes so far associated with AGS, rehearse current knowledge of the pathology as it relates to possible treatment approaches, critically appraise the potential utility of therapies, and discuss the challenges in assessing clinical efficacy.

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JAK 1/2 Blockade in MDA5 Gain-of-Function

Cited by 23 publications

References 7 publications

Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

Development and Validation of a Targeted Next-Generation Sequencing Gene Panel for Children With Neuroinflammation

Fulminant Course of Neuromyelitis Optica in a Patient With Anti-MDA5 Antibody-Positive Dermatomyositis: A Case Report

Treatments in Aicardi–Goutières syndrome

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