Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review

Amati, Francesco; Stainer, Anna; Polelli, Veronica; Mantero, Marco; Gramegna, Andrea; Blasi, Francesco; Aliberti, Stefano

doi:10.3390/ijms24097849

Cited by 23 publications

(6 citation statements)

References 30 publications

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“…Fibrosis is a major, progressive disease that afflicts the general population even in first-world countries, and very few FDA-approved therapies are available to treat a pathology that manifests as many different organ-specific diseases, such as pulmonary and hepatic fibrosis (Amati et al, 2023 ; Wollin et al, 2014 ). Only two drugs, pirfenidone and nintedanib, have been approved for the treatment of idiopathic pulmonary fibrosis, and no drugs have been approved for other fibrotic diseases.…”

Section: Discussionmentioning

confidence: 99%

Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

Tartaglia,

Fuentes,

Patel

et al. 2024

EMBO Mol Med

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Recessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.

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Section: Discussionmentioning

confidence: 99%

Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

Tartaglia,

Fuentes,

Patel

et al. 2024

EMBO Mol Med

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“…Pirfenidone is an antifibrotic agent approved by the Food and Drug Administration (FDA) for managing IPF [ 118 ]. The mechanism of action of pirfenidone in lung fibrosis involves its ability to modulate multiple pathways implicated in fibrogenesis.…”

Section: Potential Clinical Implicationsmentioning

confidence: 99%

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

Mukhatayev,

Adilbayeva,

Kunz

2024

Cells

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Pulmonary fibrosis is a chronic, progressive, irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (ECM) due to the aberrant activation of myofibroblasts in the alveolar environment. Transforming growth factor beta (TGF-β) signaling is a crucial driver of fibrogenesis because it promotes excessive ECM deposition, thereby leading to scar formation and lung damage. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in ECM deposition and wound repair. TGF-β transcriptionally regulates CTHRC1 in response to tissue injury and controls the wound healing response through functional activity. CTHRC1 may also play an essential role in re-establishing and maintaining tissue homeostasis after wound closure by modulating both the TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 regulates tissue remodeling and homeostasis. However, deregulated CTHRC1 expression in pathogenic fibroblasts has recently emerged as a hallmark of fibrosis in multiple organs and tissues. This review highlights recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, systemic sclerosis, and post-COVID-19 lung fibrosis. Notably, CTHRC1 expression is responsive to antifibrotic drugs that target the TGF-β pathway, such as pirfenidone and bexotegrast, indicating its potential as a biomarker of treatment success. These findings suggest that CTHRC1 may present new opportunities for diagnosing and treating patients with lung fibrosis.

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“…TGF-β is a central player in fibrosis, and several drug categories are designed to modulate its effects. Pirfenidone, an FDA-approved drug for IPF, inhibits TGF-β synthesis and activation [109]. It has shown effectiveness in reducing lung function decline and mortality in IPF patients [13,110].…”

Section: Targeting Cthrc1: Therapeutic Options For Lung Fibrosismentioning

confidence: 99%

CTHRC1: An Emerging Biomarker in Lung Fibrosis

Mukhatayev,

Adilbayeva,

Kunz

2023

Preprint

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Pulmonary fibrosis is a chronic, progressive, and irreversible lung disease characterized by fibrotic scarring in the lung parenchyma. This condition involves the excessive accumulation of extracellular matrix (EM) due to a persistently activated wound-repair response. The aberrant activation of myofibroblasts in the alveolar environment by Transforming Growth Factor beta (TGF-β) and other signaling molecules is considered a key event in the development and progression of fibrosis. A primary target of TGF-β signaling in fibrosis is Collagen Triple Helix Repeat Containing 1 (CTHRC1), a secreted glycoprotein that plays a pivotal role in extracellular matrix deposition. CTHRC1 is transcriptionally regulated by TGF-β and inhibits both TGF-β and canonical Wnt signaling pathways. This dual function suggests that CTHRC1 is vital in regulating tissue remodeling during wound repair. In this review, we will highlight recent studies suggesting that CTHRC1 can serve as a diagnostic and prognostic biomarker for fibrosis in idiopathic pulmonary fibrosis, rheumatoid arthritis-interstitial lung disease, systemic sclerosis, and post-COVID lung fibrosis. Notably, the expression of CTHRC1 is responsive to antifibrotic drugs such as pirfenidone indicating its potential as a therapeutic target. Collectively, these findings suggest that CTHRC1 may present new opportunities for the diagnosis, stratification, and treatment of patients with lung fibrosis.

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Efficacy of Pirfenidone and Nintedanib in Interstitial Lung Diseases Other than Idiopathic Pulmonary Fibrosis: A Systematic Review

Cited by 23 publications

References 30 publications

Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa

CTHRC1: An Emerging Hallmark of Pathogenic Fibroblasts in Lung Fibrosis

CTHRC1: An Emerging Biomarker in Lung Fibrosis

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