Novel Therapeutic Targets and Emerging Treatments for Fibrosis


Book Description

For decades we have known that the overgrowth, hardening and scarring of tissues (so-called fibrosis) represents the final common pathway and best histological predictor of disease progression in most organs. Fibrosis is the culmination of both excess extracellular matrix deposition due to ongoing or severe injury, and a failure to regenerate. An inadequate wound repair process ultimately results in organ failure through a loss of function, and is therefore a major cause of morbidity and mortality in disease affecting both multiple and individual organs. Whilst the pathology of fibrosis and its significance are well understood, until recently we have known little about its molecular regulation. Current therapies are often indirect and non-specific, and only slow progression by a matter of months. The recent identification of novel therapeutic targets, and the development of new treatment strategies based on them, offers the exciting prospect of more efficacious therapies to treat this debilitating disorder. This Research Topic therefore compromises several up-to-date mini-reviews on currently known and emerging therapeutic targets for fibrosis including: the Transforming Growth Factor (TGF)-family; epigenetic factors; Angiotensin II type 2 (AT2) receptors; mineralocorticoid receptors; adenosine receptors; caveolins; and the sphingosine kinase/sphingosine 1-phosphate and notch signaling pathways. In each case, mechanistic insights into how each of these factors contribute to regulating fibrosis progression are described, along with how they can be targeted (by existing drugs, small molecules or other mimetics) to prevent and/or reverse fibrosis and its contribution to tissue dysfunction and failure. Two additional reviews will discuss various anti-fibrotic therapies that have demonstrated efficacy at the experimental level, but are not yet clinically approved; and the therapeutic potential vs limitations of stem cell-based therapies for reducing fibrosis while facilitating tissue repair. Finally, this Research Topic concludes with a clinical perspective of various anti-fibrotic therapies for cardiovascular disease (CVD), outlining limitations of currently used therapies, the pipeline of anti-fibrotics for CVD and why so many anti-fibrotic drugs have failed at the clinical level.







Rare Diseases and Orphan Products


Book Description

Rare diseases collectively affect millions of Americans of all ages, but developing drugs and medical devices to prevent, diagnose, and treat these conditions is challenging. The Institute of Medicine (IOM) recommends implementing an integrated national strategy to promote rare diseases research and product development.




Fibrosis in Disease


Book Description

Fibroproliferative diseases are a broad spectrum of entities from organ-specific involvement (e.g., pulmonary, heart, liver, and kidney fibrosis) to multi-system diseases such as systemic sclerosis and sclerodermatous graft vs. host disease. These diseases also encompass pathophysiologies not readily recognizably related, such as macular degeneration and cancer metastasis. Fibroproliferative diseases are a leading cause of morbidity and mortality and can affect all tissues and organ systems. Remarkable progress in elucidating the pathogenesis of these common diseases with fibrotic components, including the critical roles of myofibroblasts and the molecular mechanisms driving the transcriptional activation involved in the induction of fibrosis. As the importance of these processes is realized in the long-term recovery and treatment of diseases, effective anti-fibrotic therapies targeting the underlying ongoing disease processes are lacking. The complexity of discovering and applying therapies to fibroproliferative disease may be due to the diversity of the systems the pathogenesis of disease itself involves. By nature, fibroproliferative diseases are interdisciplinary, involving multiple cell types (organ-specific epithelial cells), immune cells, endothelial cells, and fibroblasts. Bone marrow, cytokines, and organ-specific pathologies further speckle both the clinical and scientific disciplines in such a way that communication is often limited to the clinical or scientific tribes we live in, despite the greatest access to information known to man available today. Therefore, the primary focus of this text is to bring together authors from a diversity of both clinical, scientific, and therapeutic backgrounds for readers to more fully appreciate that fantastic platform that is available to build upon to lessen the isolation of the clinical and scientific disciplines. With advances in the discovery of pre-clinical therapeutic targets (at least 20+ to date) involving TGF-beta (and other cytokines), transcription factors, and downstream kinases, it’s important to both recognize the broader impact and potential opportunities that exist even today. This book will serve as a state-of-the-art resource for physicians and translational medical researchers alike who are interested in the rapidly evolving field of fibroproliferative diseases. The book will provide new insight into the fundamental mechanisms of classic fibrotic pathophysiologic processes like myocardial infarction, idiopathic pulmonary fibrosis, chronic kidney disease, wound healing, and systemic sclerosis. It will also highlight the many new areas of therapeutic investigation currently underway. Lastly, we will touch upon newly emerging fields investigating the role of fibrosis in macular degeneration and cancer metastasis. The chapters will be written by established experts in their fields, including clinicians (cardiologists, cardiovascular surgeons, pathologists, and general practitioners) and translational biomedical researchers in a wide range of disciplines. However, the material will certainly have a broader audience including medical residents, fellows, and general practitioners as well as M.D. or Ph.D. post-doctoral research fellows. While comprehensive, we'll attempt to present the material in a manner that simplifies the complex pathophysiologic mechanisms that underlie common fibroproliferative diseases while making it appealing to a broad audience.




Textbook on Scar Management


Book Description

This text book is open access under a CC BY 4.0 license. Written by a group of international experts in the field and the result of over ten years of collaboration, it allows students and readers to gain to gain a detailed understanding of scar and wound treatment – a topic still dispersed among various disciplines. The content is divided into three parts for easy reference. The first part focuses on the fundamentals of scar management, including assessment and evaluation procedures, classification, tools for accurate measurement of all scar-related elements (volume density, color, vascularization), descriptions of the different evaluation scales. It also features chapters on the best practices in electronic-file storage for clinical reevaluation and telemedicine procedures for safe remote evaluation. The second section offers a comprehensive review of treatment and evidence-based technologies, presenting a consensus of the various available guidelines (silicone, surgery, chemical injections, mechanical tools for scar stabilization, lasers). The third part evaluates the full range of emerging technologies offered to physicians as alternative or complementary solutions for wound healing (mechanical, chemical, anti-proliferation). Textbook on Scar Management will appeal to trainees, fellows, residents and physicians dealing with scar management in plastic surgery, dermatology, surgery and oncology, as well as to nurses and general practitioners







Idiopathic Pulmonary Fibrosis


Book Description

Idiopathic pulmonary fibrosis (IPF) is a steadily progressive and ultimately fatal disease of unknown origin. Recent years have seen advances in our understanding of IPF and a number of guidelines have been published. But many questions remain unanswered, particularly surrounding probable versus definite IPF. This Monograph aims to discuss the latest achievements in IPF, and covers key diagnostic issues, staging of the disease, complications and comorbidities, treatment, unmet patient needs and perspectives for the future. This book will be of interest to all clinicians and researchers in this area.










Anti-fibrotic Drug Discovery


Book Description

Fibrosis is a condition with globally high unmet medical need, and as such is a highly active area of academic and pharmaceutical research covering multiple treatment targets, organs, tissues and therapeutic approaches. Anti-fibrotic Drug Discovery is a single source reference for the latest drug-discovery approaches to tackle fibrosis in various tissues, comprehensively covering recent success and future perspectives on emerging therapeutic intervention points. The book highlights significant pre-clinical and clinical drugs currently being developed globally for this disorder. This book is ideal for postgraduate students and researchers with an interest in anti-fibrotic drug discovery as well as clinicians specialising in liver, kidney, heart and lung disease, in which fibrosis plays a key role in pathology.