Clinical perspectives into the use of thalidomide for central nervous system tuberculosis

Keddie, Stephen; Bharambe, Viraj; Jayakumar, Angelina; Shah, Arpita; Sánchez, Verónica García; Adams, Ashok; Gnanapavan, Sharmilee

doi:10.1111/ene.13732

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…In addition, previous work suggests that lenalidomide, a derivative of thalidomide, can restore T cells motility leading to their activation 26 . Finally, it was also reported that thalidomide prevents NF-kB from binding to the promoters of its target genes, including TNF-alpha and IFN-Gamma thereby reducing excessive inflammatory response 27,28 . Altogether, based on these previous studies, the reported successful use of thalidomide by Chen et al 24 , and our analysis, we hypothesize that thalidomide can be effective against COVID-2019 by modifying favourably immune response of the infected patients against the virus ( Figure 5).…”

Section: Results Sharing and Case Analysismentioning

confidence: 99%

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

Li¹,

Yu²,

Zhang³

et al. 2020

Preprint

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The COVID-2019 disease caused by the SARS-CoV-2 virus (aka 2019-nCoV) has raised significant health concerns in China and worldwide. While novel drug discovery and vaccine studies are long, repurposing old drugs against the COVID-2019 epidemic can help identify treatments, with known preclinical, pharmacokinetic, pharmacodynamic, and toxicity profiles, which can rapidly enter Phase 3 or 4 or can be used directly in clinical settings. In this study, we presented a novel network based drug repurposing platform to identify potential drugs for the treatment of COVID-2019. We first analysed the genome sequence of SARS-CoV-2 and identified SARS as the closest disease, based on genome similarity between both causal viruses, followed by MERS and other human coronavirus diseases. Using our AutoSeed pipeline (text mining and database searches), we obtained 34 COVID-2019-related genes. Taking those genes as seeds, we automatically built a molecular network for which our module detection and drug prioritization algorithms identified 24 disease-related human pathways, five modules and finally suggested 78 drugs to repurpose. Following manual filtering based on clinical knowledge, we re-prioritized 30 potential repurposable drugs against COVID-2019 (including pseudoephedrine, andrographolide, chloroquine, abacavir, and thalidomide) . We hope that this data can provide critical insights into SARS-CoV-2 biology and help design rapid clinical trials of treatments against COVID-2019.

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Section: Results Sharing and Case Analysismentioning

confidence: 99%

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

Li¹,

Yu²,

Zhang³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…93 It was concluded that thalidomide could be an alternative treatment when new influenza viruses emerge, especially before new vaccines are developed. A UK study 94 indicated that thalidomide has immuno modulatory and immune remodelling effects by inhib iting TNF, another critical cytokine in COVID-19-associated lung injury. In addition, some studies have shown that thalidomide can treat pulmonary interstitial fibrosis and combat cytokine storm.…”

Section: Thalidomidementioning

confidence: 99%

The immunology of COVID-19: is immune modulation an option for treatment?

Zhong

Tang

et al. 2020

The Lancet Rheumatology

224

238

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The coronavirus disease 2019 (COVID-19) pandemic caused by the new coronavirus (SARS-CoV-2) is currently responsible for over 500 thousand deaths in 216 countries across the world and is affecting over 10 million people. The absence of FDA approved drugs against the new SARS-CoV-2 virus has highlighted an urgent need to design new drugs. We developed an integrated model of the human cell and the SARS-CoV-2 virus to provide insight into the pathogenetic mechanism of the virus and to support current therapeutic strategies. We show the biochemical reactions required for the growth and general maintenance of the human cell, rst of all, in its healthy state. We then demonstrate how the entry of the SARS-CoV-2 virus into the human cell causes biochemical and structural changes, leading to a change of cell functions or cell death. We have completed a comparative analysis of our model and other previously generated cell type models and highlight 48 pathways and over 800 reactions hijacked by the virus for its replication and survival. We designed a new tool which predicts 15 unique reactions as drug targets from our models (the integrated human macrophage, human airway epithelial cells and the SARS-CoV2 virus) and provide a platform for future studies on viral entry inhibition and drug optimisation strategies.

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“…Recently, two clinical case studies revealed the beneficial role of thalidomide in controlling the neuroinflammation observed during CNS TB. Administration of thalidomide, in combination with anti-TB drugs and corticosteroids, was shown to improve the clinical outcome of patients with chronic TBM symptoms (Keddie et al, 2018). Another case study reported that adjunctive thalidomide (1.2 mg/kg/day) therapy with standard anti-TB drugs (HRZ) and low dose corticosteroid significantly improved the clinical status of the patient, after 5 months of treatment (Caraffa et al, 2018).…”

Section: Alternative Anti-inflammatory Drugs For Tbm Treatmentmentioning

confidence: 99%

Thalidomide and Phosphodiesterase 4 Inhibitors as Host Directed Therapeutics for Tuberculous Meningitis: Insights From the Rabbit Model

Kumar

Kolloli

Singh

et al. 2020

Front. Cell. Infect. Microbiol.

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Clinical perspectives into the use of thalidomide for central nervous system tuberculosis

Abstract: The experience gained from using thalidomide in this small case series may provide evidence leading to more research into using thalidomide to treat severe CNS TB.

Cited by 15 publications

References 15 publications

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

Network Bioinformatics Analysis Provides Insight into Drug Repurposing for COVID-2019

The immunology of COVID-19: is immune modulation an option for treatment?

Thalidomide and Phosphodiesterase 4 Inhibitors as Host Directed Therapeutics for Tuberculous Meningitis: Insights From the Rabbit Model

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