This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.

Integration of complementary and alternative medicine therapies (CAM) with conventional medicine is occurring in hospitals and physicians offices, health maintenance organizations (HMOs) are covering CAM therapies, insurance coverage for CAM is increasing, and integrative medicine centers and clinics are being established, many with close ties to medical schools and teaching hospitals. In determining what care to provide, the goal should be comprehensive care that uses the best scientific evidence available regarding benefits and harm, encourages a focus on healing, recognizes the importance of compassion and caring, emphasizes the centrality of relationship-based care, encourages patients to share in decision making about therapeutic options, and promotes choices in care that can include complementary therapies where appropriate. Numerous approaches to delivering integrative medicine have evolved. Complementary and Alternative Medicine in the United States identifies an urgent need for health systems research that focuses on identifying the elements of these models, the outcomes of care delivered in these models, and whether these models are cost-effective when compared to conventional practice settings. It outlines areas of research in convention and CAM therapies, ways of integrating these therapies, development of curriculum that provides further education to health professionals, and an amendment of the Dietary Supplement Health and Education Act to improve quality, accurate labeling, research into use of supplements, incentives for privately funded research into their efficacy, and consumer protection against all potential hazards.

The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune activation and irreversible tissueinjury that collectively exacerbate both acute and chronic pathologies. Indeed,complement dysregulation or excessive activation have been widely recognized askey pathogenic drivers in a wide spectrum of inflammatory or immune-mediateddiseases. Targeted modulation of the complement system at various points ofthe cascade has revealed promising therapeutic targets for ameliorating diseasescores in a number of conditions ranging from ocular, neurodegenerative andthromboinflammatory disorders, to cancer, periodontal diseases, chronic hemolyticanemias, ischemia-reperfusion organ injury, antibody-mediated transplant rejectionand hemodialysis-triggered inflammation. Elegant pre-clinical studies employing a diversified toolbox of highly specificcomplement inhibitors in rodent or primate models of disease have opened newavenues of therapeutic exploration by providing proof of concept for the therapeuticefficacy of complement modulation. At the same time, the clinical experience gainedduring this last decade with the sole complement-specific drug currently in the clinic,eculizumab, has rekindled the interest of biopharmaceutical companies in developingnew and potent complement therapeutics for complement-driven diseases. In this respect, the complement field is witnessing a new surge of clinical trialsthat are evaluating the safety, PK/PD profile and clinical efficacy of promising drugcandidates in a number of clinical conditions driven by complement imbalance orover-activation.

From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators in vivo are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate! Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious. - Complement regulators--structure, functional roles and mode of action - Comprehensive reviews of each of the individual regulators - Roles of Complement regulators in vivo,in health and disease: - Consequences of deficiency - Roles in the reproductive system - Interactions with pathogens - Exploitation for therapy - Complement regulators in other species

Actively reflecting conventional medical treatment objectives, interactions, benefits, and risks, this book is presented in a format that patients can easily understand and that oncologists can confidently recommend to their patients.