A useful introduction to a rapidly advancing field

Abstract

Gene Therapy in Inflammatory Diseasesedited by C.H. Evans and P.D. Robbins,Birkhauser, 2000. $145.00 hbk (272 pages)ISBN 3 7643 5855 6Chronic inflammatory diseases, including asthma, rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease (IBD) and many autoimmune diseases, are a major burden and account for a considerable proportion of healthcare spending in industrialized countries. Despite differences in clinical manifestation between these diseases, there are many common features to the underlying inflammatory processes. There have been major advances in understanding the molecular mechanisms involved in these diseases, and major efforts have been directed towards finding more specific, more effective and safer anti-inflammatory drugs, based on existing or novel molecular targets. In view of the huge expenditure on drug therapy for these diseases, it is hardly surprising that gene therapy approaches are now being explored. All of these inflammatory diseases are polygenic, so that gene therapy is not designed to replace a malfunctioning gene but is used to deliver an anti-inflammatory or immunosuppressive treatment. This is the first book devoted to the subject of gene therapy in inflammatory diseases. The book only considers chronic diseases, as acute inflammatory conditions such as septic shock, which require rapid effects, are probably not suitable diseases for gene therapy.This book discusses the potential for gene therapy in a number of chronic inflammatory diseases, with a particular emphasis on RA, but also covering allergic airways inflammation, Sjogren's syndrome, lupus erythematosis, multiple sclerosis, diabetes and transplantation. However, IBD, skin diseases and atherosclerosis (one of the most common chronic inflammatory diseases) are not covered. As only preliminary clinical data are available at present, the chapters focus on research in animal models, with the local or systemic delivery of genes encoding various anti-inflammatory proteins, such as interleukin (IL)-10, IL-1 receptor antagonist, inhibitor of nuclear factor-κB (IκB-α), soluble receptors to proinflammatory cytokines and Fas-ligand, used to induce apoptosis of inflammatory cells. The key issue of local versus systemic delivery is discussed and several studies suggest that local delivery, for example to a joint, can have systemic effects. The use of tissue-specific promoters might result in a more localized expression of particular genes at the site of the disease. This approach is attractive if long-term gene delivery becomes possible. The idea of increased therapeutic gene expression, via inflammation-induced promoters in the gene construct, is attractive, as the level of expression could then be regulated by disease activity.Although gene therapy for the long-term treatment of chronic inflammatory diseases holds much promise, there are major barriers to overcome before this approach is realistic in a clinical setting. In particular, there are major problems with gene delivery, as most methods are either grossly inefficient or are associated with adverse effects, such as the inflammatory response induced by adenovirus. There are also problems with the persistence of gene expression and the immune response to the exogenous gene and its product, which still present major barriers. There have been important advances in the design of viral vectors, and of particular interest is the use of DNA vaccination with genes for allergens or cytokines, which is discussed in a separate chapter.This book gives a good overview of the approaches that are being taken to develop gene therapy for chronic inflammatory diseases. It discusses the various ways of delivering genes and their limitations. This is a rapidly advancing field, so any book is bound to be out of date as soon as it is published but it does provide useful background material on an exciting area that will undoubtedly blossom in the future.