Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study

Background: Keloids are an abnormal proliferation of scars that can involve large areas of tissue beyond the original injury site. Hypertrophic scars are similar clinically, but do not exceed the original scar limits. These scarring abnormalities can cause noxious symptoms such as pain, tenderness, itching, and ulcerations. The aim of this review is to discuss current therapies for both types of abnormal scarring, and to determine if guidelines can be provided for excisional treatment with adjuvant therapies versus non-excisional methods. Methods: A systematic literature search was performed through the Web of Science database. The search revolved around keywords such as “keloid,” “hypertrophic scars,” and “treatment.” Articles were reviewed and screened for inclusion and exclusion criteria. The review focuses on an analysis and summarization of randomized control trials regarding keloid or hypertrophic scar treatments. Results: The original searches produced 1161 and 1275 articles for keloid and hypertrophic scars, respectively. In total, 316 duplicates were found. After accounting for 2014–2019 publication time, 655 keloid and 893 hypertrophic scar articles were reviewed. This resulted in 15 articles that pertained to treatment and randomized control trials. Conclusions: Keloids and hypertrophic scars present a clinical challenge. Based on qualitative review of recurrence, neither excision plus adjuvant therapy or nonsurgical treatments can be recommended preferentially at this time. More research is needed to determine if recurrence rate bias exists between the treatment regimens, as excisional treatment plus adjuvant therapy is reserved for refractory scars.

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“…Per Patient and Observer Scar Assessment Scale score, scar severity was reduced by 86% with anti-connective tissue growth factor. 3 …”

Section: Resultsmentioning

confidence: 99%

Scoping Review of Therapeutic Strategies for Keloids and Hypertrophic Scars

Anderson

Foglio

Harrant

et al. 2021

Plastic and Reconstructive Surgery - Global Open

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“…An antisense oligonucleotide (EXC-001) has been developed to inhibit CTGF production and reduce CTGF-driven collagen deposition and scar formation (Jensen et al, 2018). The mechanism of EXC-001 action is to bind to CTGF mRNA and inhibit the expression of CTGF protein.…”

Section: Sirnas and Asosmentioning

confidence: 99%

Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery

Chen

Zhang

Chu

et al. 2020

Front. Cell Dev. Biol.

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Connective tissue growth factor (CTGF) is a key signaling and regulatory molecule involved in different biological processes, such as cell proliferation, angiogenesis, and wound healing, as well as multiple pathologies, such as tumor development and tissue fibrosis. Although the underlying mechanisms of CTGF remain incompletely understood, a commonly accepted theory is that the interactions between different protein domains in CTGF and other various regulatory proteins and ligands contribute to its variety of functions. Here, we highlight the structure of each domain of CTGF and its biology functions in physiological conditions. We further summarized main diseases that are deeply influenced by CTGF domains and the potential targets of these diseases. Finally, we address the advantages and disadvantages of current drugs targeting CTGF and provide the perspective for the drug discovery of the next generation of CTGF inhibitors based on aptamers.

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“…TGF-b1 is the best characterized among them, functioning as an anti-inflammatory and profibrotic cytokine that has been demonstrated to shift the muscle injury response toward fibrosis (28). TGF-b1 binds to a complex of TGF-BRI and dimers of the TGFBRII receptor families, which activate SMADs 2/3 and connective tissue growth factor (CTGF) expression, along with NF-kB inhibition and antiinflammatory effects downstream (28)(29)(30)(31)(32).This activates FAP transformation into fibroblasts, fibroblast proliferation, and deposition of ECM products like collagen I and III (28,33). In skeletal muscle injury, increased myofiber TGF-b1 expression has been shown to result in increased fibrosis whereas myofiber-specific deletion of the TGFBRII receptor is protective against fibrosis (30,34,35).…”

mentioning

confidence: 99%

Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis

Stepien

Hwang

Marini

et al. 2020

The Journal of Immunology

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Myeloid cells are critical to the development of fibrosis following muscle injury; however, the mechanism of their role in fibrosis formation remains unclear. In this study, we demonstrate that myeloid cell-derived TGF-b1 signaling is increased in a profibrotic ischemia reperfusion and cardiotoxin muscle injury model. We found that myeloid-specific deletion of Tgfb1 abrogates the fibrotic response in this injury model and reduces fibro/adipogenic progenitor cell proliferation while simultaneously enhancing muscle regeneration, which is abrogated by adaptive transfer of normal macrophages. Similarly, a murine TGFBRII-Fc ligand trap administered after injury significantly reduced muscle fibrosis and improved muscle regeneration. This study ultimately demonstrates that infiltrating myeloid cell TGF-b1 is responsible for the development of traumatic muscle fibrosis, and its blockade offers a promising therapeutic target for preventing muscle fibrosis after ischemic injury.

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Anti-CTGF Oligonucleotide Reduces Severity of Postsurgical Hypertrophic Scars in a Randomized, Double-Blind, Within-Subject, Placebo-Controlled Study

Abstract: Therapeutic, II.

Cited by 21 publications

References 11 publications

Scoping Review of Therapeutic Strategies for Keloids and Hypertrophic Scars

Scoping Review of Therapeutic Strategies for Keloids and Hypertrophic Scars

Connective Tissue Growth Factor: From Molecular Understandings to Drug Discovery

Tuning Macrophage Phenotype to Mitigate Skeletal Muscle Fibrosis

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