The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease

Gupta, Nancy; Papasotiriou, Sam; Hanauer, Stephen B.

doi:10.1080/1744666x.2023.2214728

Cited by 4 publications

(2 citation statements)

References 58 publications

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“…Key down-stream signaling molecules in this pathway are Janus kinases (JAK). In fact, JAK inhibitors have emerged for controlling the above described autoimmune/autoinflammatory conditions triggered by type 1 IFN signaling ( 168 , 169 ). In this section, JAK inhibitors and Th17 cell targeted treatment measures will be discussed.…”

Section: Immunomodulating Agents Utilized For Autoimmune/autoinflamma...mentioning

confidence: 99%

“…In ASD subjects with pre-existing immunodysregulatory conditions involving the JAK/STAT pathways, JAK inhibitor may provide an additional treatment option for controlling neuropsychiatric symptoms, especially in those suffering from long COVID. Oral intake and the acceptable safety profiles of JAK inhibitors may make it an easier option for ASD subjects ( 168 , 169 ).…”

Section: Immunomodulating Agents Utilized For Autoimmune/autoinflamma...mentioning

confidence: 99%

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Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Jyonouchi

2024

Front. Psychiatry

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Autism spectrum disorder (ASD1) is a behaviorally defined syndrome encompassing a markedly heterogeneous patient population. Many ASD subjects fail to respond to the 1st line behavioral and pharmacological interventions, leaving parents to seek out other treatment options. Evidence supports that neuroinflammation plays a role in ASD pathogenesis. However, the underlying mechanisms likely vary for each ASD patient, influenced by genetic, epigenetic, and environmental factors. Although anti-inflammatory treatment measures, mainly based on metabolic changes and oxidative stress, have provided promising results in some ASD subjects, the use of such measures requires the careful selection of ASD subjects based on clinical and laboratory findings. Recent progress in neuroscience and molecular immunology has made it possible to allow re-purposing of currently available anti-inflammatory medications, used for autoimmune and other chronic inflammatory conditions, as treatment options for ASD subjects. On the other hand, emerging anti-inflammatory medications, including biologic and gate-keeper blockers, exert powerful anti-inflammatory effects on specific mediators or signaling pathways. It will require both a keen understanding of the mechanisms of action of such agents and the careful selection of ASD patients suitable for each treatment. This review will attempt to summarize the use of anti-inflammatory agents already used in targeting ASD patients, and then emerging anti-inflammatory measures applicable for ASD subjects based on scientific rationale and clinical trial data, if available. In our experience, some ASD patients were treated under diagnoses of autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. However, there are little clinical trial data specifically for ASD subjects. Therefore, these emerging immunomodulating agents for potential use for ASD subjects will be discussed based on preclinical data, case reports, or data generated in patients with other medical conditions. This review will hopefully highlight the expanding scope of immunomodulating agents for treating neuroinflammation in ASD subjects.

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Section: Immunomodulating Agents Utilized For Autoimmune/autoinflamma...mentioning

confidence: 99%

Section: Immunomodulating Agents Utilized For Autoimmune/autoinflamma...mentioning

confidence: 99%

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Jyonouchi

2024

Front. Psychiatry

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Understanding the molecular mechanisms of anti-trafficking therapies and their clinical relevance in inflammatory bowel disease

et al. 2023

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JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

Sarapultsev,

Gusev,

Komelkova

et al. 2023

Mol Biomed

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The Janus kinase-signal transducer and transcription activator pathway (JAK-STAT) serves as a cornerstone in cellular signaling, regulating physiological and pathological processes such as inflammation and stress. Dysregulation in this pathway can lead to severe immunodeficiencies and malignancies, and its role extends to neurotransduction and pro-inflammatory signaling mechanisms. Although JAK inhibitors (Jakinibs) have successfully treated immunological and inflammatory disorders, their application has generally been limited to diseases with similar pathogenic features. Despite the modest expression of JAK-STAT in the CNS, it is crucial for functions in the cortex, hippocampus, and cerebellum, making it relevant in conditions like Parkinson's disease and other neuroinflammatory disorders. Furthermore, the influence of the pathway on serotonin receptors and phospholipase C has implications for stress and mood disorders. This review expands the understanding of JAK-STAT, moving beyond traditional immunological contexts to explore its role in stress-related disorders and CNS function. Recent findings, such as the effectiveness of Jakinibs in chronic conditions such as rheumatoid arthritis, expand their therapeutic applicability. Advances in isoform-specific inhibitors, including filgotinib and upadacitinib, promise greater specificity with fewer off-target effects. Combination therapies, involving Jakinibs and monoclonal antibodies, aiming to enhance therapeutic specificity and efficacy also give great hope. Overall, this review bridges the gap between basic science and clinical application, elucidating the complex influence of the JAK-STAT pathway on human health and guiding future interventions. Graphical Abstract

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The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease

Cited by 4 publications

References 58 publications

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Understanding the molecular mechanisms of anti-trafficking therapies and their clinical relevance in inflammatory bowel disease

JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions

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