Universal Antibrotic Therapies:

Targeting Fibrotic Tissue Across Organs

Ian Y.H. Chua

1, 2, 3, 4

18 February 2025

Abstract

Fibrosis, characterized by excessive deposition of extracellular matrix (ECM), is a

hallmark of chronic diseases aecting various organs, including the liver, lungs, kidneys,

and heart. Current antibrotic therapies often target specic organs, leading to high

development costs and limited applicability across multiple brotic conditions.

Developing universal antibrotic drugs that specically target brotic tissues or brosis-

causing cells, regardless of organ location, presents a cost-eective and broadly

applicable solution. This paper explores the pathophysiological commonalities of

brosis across organs, reviews current universal antibrotic strategies, and examines

emerging therapies designed to act selectively on brotic tissue. Evidence from recent

studies underscores the potential for these universal treatments to revolutionize brosis

management across multiple organ systems.

Introduction

Fibrosis contributes to nearly 45% of deaths in developed countries due to its

involvement in chronic organ failure, including liver cirrhosis, idiopathic pulmonary

brosis (IPF), chronic kidney disease (CKD), and cardiac brosis [1]. Despite its

prevalence, current treatments predominantly focus on organ-specic pathways,

leading to high costs and limited accessibility [2]. Universal antibrotic therapies that act

on common brosis pathways across dierent organs could reduce development

expenses and improve treatment accessibility [3]. Such therapies should ideally target

activated broblasts or myobroblasts and the ECM, thereby acting selectively on

brotic tissue without harming healthy cells [4].

Pathophysiological Similarities in Fibrosis Across Organs

Fibrosis development follows a common sequence of chronic injury, inammation,

broblast activation, and ECM deposition [5]. Key pathways include transforming growth

factor-beta (TGF-β), platelet-derived growth factor (PDGF), and connective tissue growth

factor (CTGF), which are consistently upregulated in brotic tissues regardless of organ

origin [6]. Targeting these shared pathways provides a foundation for developing broad-

spectrum antibrotic therapies [7].

Current Universal Antibrotic Strategies

TGF-β Inhibitors

TGF-β is a master regulator of brosis. Agents like fresolimumab, a monoclonal antibody

targeting TGF-β, have demonstrated antibrotic eects in various organ systems [8].

Clinical trials show its potential in both renal and pulmonary brosis, emphasizing its

cross-organ applicability [9].

Connective Tissue Growth Factor (CTGF) Blockers

Pamrevlumab, a CTGF inhibitor, has shown promising results in treating both IPF and

pancreatic brosis, suggesting its broader antibrotic potential [10]. Targeting CTGF can

inhibit broblast activation and ECM production across tissues [11].

Anti-Fibroblast Activation Protein (FAP) Therapies

FAP is highly expressed on activated broblasts in brotic tissues but not in healthy cells,

making it an ideal target. Monoclonal antibodies and FAP-targeting CAR-T cells are under

investigation for their universal antibrotic properties [12].

Emerging Therapies Targeting Fibrotic Tissue Across Organs

Senolytics

Senescent cells contribute to brosis by secreting pro-brotic factors. Senolytic agents

like dasatinib and quercetin have shown eicacy in reducing brosis in lung, liver, and

kidney models [13]. Their ability to target senescent cells irrespective of organ location

highlights their universal potential [14].

Matrix Metalloproteinase (MMP) Modulators

MMPs regulate ECM turnover. Modulating MMP activity can prevent excessive ECM

accumulation. Agents like marimastat have been explored for their antibrotic potential

across dierent tissues [15].

Nanoparticle-Based Delivery Systems

Engineered nanoparticles can deliver antibrotic drugs directly to brotic tissues by

exploiting overexpressed markers like integrins. These systems improve drug

accumulation at brotic sites while minimizing o-target eects [16].

Advantages of Universal Antibrotic Therapies

• Cost-Eectiveness: Developing a single drug for multiple brotic conditions

reduces research and manufacturing expenses [17].

• Broad Applicability: Patients with multi-organ brosis can benet from a unied

treatment approach [18].

• Simplied Clinical Trials: Universal targets like FAP and TGF-β streamline

clinical evaluation across various brosis-related diseases [19].

Challenges and Future Directions

While universal antibrotics hold promise, challenges include ensuring tissue selectivity

to avoid disrupting normal wound healing and tissue repair processes [20]. Future

research should focus on identifying biomarkers that enhance targeting specicity and

minimize side eects [21].

Conclusion

Universal antibrotic therapies targeting common pathways and brotic tissues across

organs oer a cost-eective and eicient approach to managing brosis. By focusing on

shared mechanisms like broblast activation and ECM deposition, these treatments

have the potential to transform care for patients with diverse brotic conditions.

Continued research into molecular targets, delivery systems, and patient-specic

factors will be crucial in bringing these therapies to clinical practice.

Acknowledgments

This paper was developed with the assistance of ChatGPT 4.0, which provided insights and renements in the

articulation of philosophical and scientic concepts.

Founder/CEO, ACE-Learning Systems Pte Ltd.

M.Eng. Candidate, Texas Tech University, Lubbock, TX.

M.S. (Anatomical Sciences Education) Candidate, University of Florida College of Medicine, Gainesville, FL.

M.S. (Medical Physiology) Candidate, Case Western Reserve University School of Medicine, Cleveland, OH.

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