Pirfenidone gel in patients with localized scleroderma: a phase II study

Rodríguez‐Castellanos, Marco Antonio; Tlacuilo‐Parra, Alberto; Sánchez‐Enríquez, Sergio; Vélez-Gómez, Ezequiel; Guevara‐Gutiérrez, Elizabeth

doi:10.1186/s13075-014-0510-4

Cited by 37 publications

(34 citation statements)

References 24 publications

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“…A recent clinical trial by Armendariz-Borunda et al [27] shows that topical administration of 8 % PFD gels is effective and safe in the treatment of hypertrophic scars caused by burns in children. Another recent study by Rodríguez-Castellanos et al [50] shows that topical application of 8 % PFD gels to localized scleroderma reduces both inflammation and fibrosis. These studies raise the prospect of using PFD locally in DD patients rather than via systemic oral administration.…”

Section: Discussionmentioning

confidence: 99%

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Zhou

Liu

Gallo

et al. 2016

BMC Musculoskelet Disord

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BackgroundDupuytren’s disease (DD) is a complex fibro-proliferative disorder of the hand that is often progressive and eventually can cause contractures of the affected fingers. Transforming growth factor beta (TGF-β1) has been implicated as a key stimulator of myofibroblast activity and fascial contraction in DD. Pirfenidone (PFD) is an active small molecule shown to inhibit TGF-β1-mediated action in other fibrotic disorders. This study investigates the efficacy of PFD in vitro in inhibiting TGF-β1-mediated cellular functions leading to Dupuytren’s fibrosis.MethodsFibroblasts harvested from (DD) and carpal tunnel (CT)- tissues were treated with or without TGF-β1 and/or PFD and were subjected to cell migration, cell proliferation and cell contraction assays. ELISA; western blots and real time RT-PCR assays were performed to determine the levels of fibronectin; p-Smad2/Smad3; alpha-smooth muscle actin (α-SMA), α2 chain of type I collagen and α1 chain of type III collagen respectively.ResultsOur results show that PFD effectively inhibits TGF-β1-induced cell migration, proliferation and cell contractile properties of both CT- and DD-derived fibroblasts. TGF-β1−induced α-SMA mRNA and protein levels were inhibited at the higher concentration of PFD (800 μg/ml). Interestingly, TGF-β1 induction of type I and type III collagens and fibronectin was inhibited by PFD in both CT- and DD- derived fibroblasts, but the effect was more prominent in DD cells. PFD down-regulated TGF-β1-induced phosphorylation of Smad2/Smad3, a key factor in the TGF-β1 signaling pathway.ConclusionTaken together these results suggest the PFD can potentially prevent TGF-β1−induced fibroblast to myofibroblast transformation and inhibit ECM production mainly Type I- and Type III- collagen and fibronectin in DD-derived fibroblasts. Further in-vivo studies with PFD may lead to a novel therapeutic application in preventing the progression or recurrence of Dupuytren’s disease.

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Section: Discussionmentioning

confidence: 99%

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Zhou

Liu

Gallo

et al. 2016

BMC Musculoskelet Disord

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“…In different model systems it has been shown to abrogate TGF-β1-stimulated collagen synthesis by inhibiting the upregulation of HSP47 and Col1 RNA, it blocks the proliferative effects of PDGF; reduces fibroblast proliferation and downregulates the proinflammatory cytokines, TNFα, IFNγ, IL-1B and IL-6. 116 Topical application has been studied in human scleroderma 117 and in glaucoma scarring models. 118 Finally, the topical use of anti-inflammatory monoclonal antibodies, such as the anti TNFα drugs that could be given subconjunctivally, should be evaluated.…”

Section: Topical Therapies For Inflammation and Scarringmentioning

confidence: 99%

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Dart

2017

Eye

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This review is in two sections. The first section summarises 35 conditions, both common and infrequent, causing cicatrising conjunctivitis. Guidelines for making a diagnosis are given together with the use of diagnostic tests, including direct and indirect immunofluorescence, and their interpretation. The second section evaluates our knowledge of ocular mucous membrane pemphigoid, which is the commonest cause of cicatrizing conjunctivitis in most developed countries. The clinical characteristics, demographics, and clinical signs of the disease are described. This is followed by a review and re-evaluation of the pathogenesis of conjunctival inflammation in mucous membrane pemphigoid (MMP), resulting in a revised hypothesis of the autoimmune mechanisms causing inflammation in ocular MMP. The relationship between inflammation and scarring in MMP conjunctiva is described. Recent research, describing the role of aldehyde dehydrogenase (ALDH) and retinoic acid (RA) in both the initiation and perpetuation of profibrotic activity in MMP conjunctival fibroblasts is summarised and the potential for antifibrotic therapy, using ALDH inhibition, is discussed. The importance of the management of the ocular surface in MMP is briefly summarised. This is followed with the rationale for the use of systemic immunomodulatory therapy, currently the standard of care for patients with active ocular MMP. The evidence for the use of these drugs is summarised and guidelines given for their use. Finally, the areas for research and innovation in the next decade are reviewed including the need for better diagnostics, markers of disease activity, and the potential for biological and topical therapies for both inflammation and scarring.

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“…Furthermore, the authors noted that dyspnoea was attenuated in three patients, along with a reduction in ground-glass shadowing seen on the chest imaging of two patients. In another study of 12 patients, the potential benefits of topical pirfenidone in patients with localised scleroderma (morphoea) were demonstrated, with significant improvements seen in skin scores (p = 0.002) and histopathological markers (p = 0.032) at 6 months [44].…”

Section: Tgf-β Pathway Inhibitorsmentioning

confidence: 96%

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

Russell¹,

Sofat²

2017

Immunopathogenesis and Immune-Based Therapy for Selected Autoimmune Disorders

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Targeted therapies including tumour necrosis factor α (TNFα) inhibitors have transformed the management of a number of autoimmune conditions over the past 20 years. One autoimmune rheumatological condition with significant potential for the development of targeted therapies is systemic sclerosis (SSc). In this chapter, we use SSc as an example of how research into the pathogenic processes underlying autoimmune conditions can be translated into novel targeted therapies. We review the evidence base for a range of targeted therapies for SSc identified from a systematic literature search, before highlighting a number of studies currently underway.

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Pirfenidone gel in patients with localized scleroderma: a phase II study

Cited by 37 publications

References 24 publications

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

Anti-fibrotic action of pirfenidone in Dupuytren’s disease-derived fibroblasts

The 2016 Bowman Lecture Conjunctival curses: scarring conjunctivitis 30 years on

Translating Autoimmune Pathogenesis into Targeted Therapies for Systemic Sclerosis

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