Systemic lupus erythematosus

Kaul, Arvind; Gordon, Caroline; Crow, Mary K.; Touma, Zahi; Urowitz, Murray B.; Vollenhoven, Ronald van; Ruiz‐Irastorza, Guillermo; Hughes, G. R. V.

doi:10.1038/nrdp.2016.39

Cited by 965 publications

(835 citation statements)

References 194 publications

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“…This reflects the multifactorial aetiology of this disorder, which involves both a microbial or epithelial and an autoimmune component 218 , and suggests that autophagy activators may be beneficial for patients with Crohn’s disease. Indeed, everolimus ameliorated disease severity in Il10 −/− mice, which spontaneously develop a Crohn’s disease-like syndrome 219 .…”

Section: Autophagy As a Therapeutic Targetmentioning

confidence: 95%

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Galluzzi

Pedro

Levine

et al. 2017

Nat Rev Drug Discov

716

589

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Autophagy is central to the maintenance of organismal homeostasis in both physiological and pathological situations. Accordingly, alterations in autophagy have been linked to clinically relevant conditions as diverse as cancer, neurodegeneration and cardiac disorders. Throughout the past decade, autophagy has attracted considerable attention as a target for the development of novel therapeutics. However, such efforts have not yet generated clinically viable interventions. In this Review, we discuss the therapeutic potential of autophagy modulators, analyse the obstacles that have limited their development and propose strategies that may unlock the full therapeutic potential of autophagy modulation in the clinic.

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Section: Autophagy As a Therapeutic Targetmentioning

confidence: 95%

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Galluzzi

Pedro

Levine

et al. 2017

Nat Rev Drug Discov

716

589

View full text Add to dashboard Cite

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“…A hallmark feature of human SLE is the presence of ANAs, anti-dsDNA antibodies and anti-RNA or RNA-associated antibodies. Clinical manifestations include GN, arthritis, heart disease, cutaneous lesions and neurological symptoms [1]. Likewise, as each patient presents with a unique phenotype, mouse models can recapitulate only limited features of the disease (Table 1).…”

Section: Main Mouse Modelsmentioning

confidence: 99%

“…SLE is a complex autoimmune disease with an extremely heterogeneous clinical presentation, which reflects the multiple roles of the environment, genetics and immune response in disease initiation and progression [1]. Variability in disease manifestation and severity makes it extremely challenging to study in clinical trials, especially in terms of selecting the patient population who will be most likely to respond to the treatment under investigation [2].…”

Section: Introductionmentioning

confidence: 99%

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

Celhar

Fairhurst

2016

Rheumatology

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Mouse models of SLE have been indispensable tools to study disease pathogenesis, to identify genetic susceptibility loci and targets for drug development, and for preclinical testing of novel therapeutics. Recent insights into immunological mechanisms of disease progression have boosted a revival in SLE drug development. Despite promising results in mouse studies, many novel drugs have failed to meet clinical end points. This is probably because of the complexity of the disease, which is driven by polygenic predisposition and diverse environmental factors, resulting in a heterogeneous clinical presentation. Each mouse model recapitulates limited aspects of lupus, especially in terms of the mechanism underlying disease progression. The main mouse models have been fairly successful for the evaluation of broad-acting immunosuppressants. However, the advent of targeted therapeutics calls for a selection of the most appropriate model(s) for testing and, ultimately, identification of patients who will be most likely to respond.

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“…SLE is a chronic autoimmune disorder that can affect several organs with a significant unmet medical need 25 . It is a complex and remarkably heterogeneous disease, in terms of both genetics and clinical manifestations 26 .…”

Section: Workflowmentioning

confidence: 99%

Using regulatory genomics data to interpret the function of disease variants and prioritise genes from expression studies

Ferrero

2018

F1000Res

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The identification of therapeutic targets is a critical step in the research and developement of new drugs, with several drug discovery programmes failing because of a weak linkage between target and disease. Genome-wide association studies and large-scale gene expression experiments are providing insights into the biology of several common and complex diseases, but the complexity of transcriptional regulation mechanisms often limit our understanding of how genetic variation can influence changes in gene expression. Several initiatives in the field of regulatory genomics are aiming to close this gap by systematically identifying and cataloguing regulatory elements such as promoters and enhacers across different tissues and cell types. In this Bioconductor workflow, we will explore how different types of regulatory genomic data can be used for the functional interpretation of disease-associated variants and for the prioritisation of gene lists from gene expression experiments.

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Systemic lupus erythematosus

Cited by 965 publications

References 194 publications

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Pharmacological modulation of autophagy: therapeutic potential and persisting obstacles

Modelling clinical systemic lupus erythematosus: similarities, differences and success stories

Using regulatory genomics data to interpret the function of disease variants and prioritise genes from expression studies

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