Emerging targets for the treatment of scleroderma

  title={Emerging targets for the treatment of scleroderma},
  author={Andrew Leask},
  journal={Expert Opinion on Emerging Drugs},
  pages={173 - 179}
  • A. Leask
  • Published 25 May 2012
  • Medicine, Biology
  • Expert Opinion on Emerging Drugs
Introduction: Scleroderma is an often-fatal autoimmune connective tissue disease. Recommendations for treating digital ulcers and pulmonary hypertension in scleroderma have recently been established by the European League Against Rheumatism. Conversely, although many valuable insights have been generated into the molecular mechanism underlying the persistent fibrotic phenotype in scleroderma, no safe, clinically proven effective treatment has been found for this aspect of the disease. Areas… 

Nox isoforms in thickened tissue

Strong immunohistochemical evidence of Nox4 protein has been demonstrated in the alveolar epithelial layer and thickened pulmonary artery in fibrotic scars of lung specimens taken from patients with idiopathic pulmonary fibrosis, suggesting that Nox 4 acts as an effector in the profibrotic signalling axis of TGFb in dermal fibroblasts, cells that are engaged in cutaneous fibrosis and systemic sclerosis.

Serotonin and Scleroderma

Study on the relationship between 5-HT and scleroderma will inaugurate a new way for the treatment of sclerodma.

Connective tissue growth factor in tissue fibrosis

It is shown that CTGF plays a pivotal role in fibrosis and blocking CTGF activity may be useful as a specific target of attenuating fibrosis in SSc, and the reduction or absence of CTGF could abrogate fibrosis.

Involvement of collagen-binding heat shock protein 47 in scleroderma-associated fibrosis

The results in this study provide direct evidence that HSP47 is involved in the pathogenesis of scleroderma, and the high expression of HSP 47 can be detected in the circulatory system of scleroderma patients, indicating that H SP47 may become a pathological marker to assess the progression of sclerosis, and also explain the systemic fibrosis of s cleroderma.

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

  • A. HaakP. Tsou R. Neubig
  • Biology, Medicine
    The Journal of Pharmacology and Experimental Therapeutics
  • 2014
Targeting the MRTF/SRF gene transcription pathway could provide an efficacious new approach to therapy for SSc and other fibrotic disorders.

Immunological and autoimmune considerations of Autism Spectrum Disorders.

Drug Target Prediction and Repositioning Using an Integrated Network-Based Approach

A network-based approach for the prediction of drug targets for a given disease and the ability of the method to identify non-suspected repositioning candidates using diabetes type 1 as an example is demonstrated.

Dynamics of Transforming Growth Factor Beta Signaling in Wound Healing and Scarring.

The challenge of translating preclinical studies targeting the TGF-β signaling pathway to a clinical setting may require more extensive preclinical research using animal models that more closely mimic wound healing and scarring in humans, and taking into account the spatial, temporal, and cell-type-specific aspects of T GF-β isoform expression and function.

Elastin and collagen fibre microstructure of the human aorta in ageing and disease: a review

The state of the art with respect to characterization of connective fibre microstructure in the wall of the human aorta in ageing and disease is summarized, with emphasis on the ascending thoracic aorti and abdominal aortas where the most common forms of aortic disease tend to occur.

Juvenile zirkumskripte Sklerodermie

Die Therapie ist abhangig von der Lokalisation, Verteilung and Progress der Erkrankung and umfasst bei milderen aktiven Formen den topischen Einsatz of Kortikosteroiden, Vitamin-D-Derivaten and Calcineurininhibitoren.



Targeted therapy comes of age in scleroderma.

New developments in localized scleroderma

  • F. Zulian
  • Medicine
    Current opinion in rheumatology
  • 2008
Studies over the past year highlight the role of some outcome measures in the disease assessment and monitoring, with important implications both for the clinical practice and future clinical trials.

B cell block: is rituximab a new possible treatment for systemic sclerosis?

  • A. Leask
  • Medicine, Biology
    Journal of Cell Communication and Signaling
  • 2010
In a recent report by Bosello and colleagues, rituximab was tolerated in SSc patients and appeared to result in an improvement of the skin score and of clinical symptoms of SSc, one of a series of recent studies suggesting that ritUXimab may be a possible treatment for SSc.

Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets.

Capillary Regeneration in Scleroderma: Stem Cell Therapy Reverses Phenotype?

The first objective evidence for loss of vessels in scleroderma is provided and this phenomenon is reversible, suggesting that control of expression of these three molecules may be the underlying mechanism for at least the vascular component of this disease.

Molecular Subsets in the Gene Expression Signatures of Scleroderma Skin

Genome-wide gene expression profiling of skin biopsies demonstrates that the heterogeneity in scleroderma can be measured quantitatively with DNA microarrays and the diversity in gene expression demonstrates multiple distinct gene expression programs in the skin of patients with sclerodma.

The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab

Softening of the skin was observed during the treatment with tocilizumab in the two cases of SSc that are reported here, and Histological examination showed thinning of the collagen fibre bundles in the dermis.

Skin involvement in scleroderma--where histological and clinical scores meet.

The histological extent of skin fibrosis correlates closely with the mRSS, and the extent of TGF-beta signalling activation in SSc skin fibroblasts appears to parallel the severity of disease.

Systemic sclerosis: an autoantibody mosaic

  • BunnBlack
  • Medicine
    Clinical and experimental immunology
  • 1999
Serologically, however, several different autoantibodies occur in non-overlapping populations that in general correlate with prognosis and suggest that SSc could be a composite of distinct clinical entities.

EULAR recommendations for the treatment of systemic sclerosis: a report from the EULAR Scleroderma Trials and Research group (EUSTAR)

Evidence-based, consensus-derived recommendations for the treatment of systemic sclerosis are useful for rheumatologists to help guide treatment for patients with SSc and may also help to define directions for future clinical research in SSc.