Gaucher Disease PDF

Preface

Gaucher disease is a multi-system disease that was first described by the French physician Philippe Gaucher in 1882. Since this first clinical description, there have been tremendous advances in our understanding of Gaucher disease pathology, progression, and management. It has been known for about 50 years that Gaucher disease belongs to a group of human inherited diseases classified as lysosomal storage disorders (LSDs), which are caused by the defective activity of one or more enzymes found in the lysosome. Gaucher disease is the most common LSD and often acts as a prototype for the others, inasmuch as many of the treatments now available for LSDs were first tested and their efficacy shown in Gaucher disease; this is true for enzyme replacement therapy (ERT), substrate reduction therapy (SRT), bone marrow therapy, and other new and emerging therapies, some of which are discussed in this book.

Part of the stimulus for writing this book at this time comes from the recent renewal of interest in the underlying biochemical mechanisms responsible for Gaucher disease pathology. In 1982, when the first book dedicated to Gaucher disease was published by Desnick, Gatt, and Grabowski ( Gaucher Disease: A Century of Delineation and Research , Desnick, R.J., Gatt, S., and Grabowski, G.A., eds., New York, Alan R. Liss), little basic science was included and there was still no therapy for the disease. When a more recent book was published in 1997 (Gaucher's Disease. In Clinical Haematology , Zimran, A, ed., Balliere Tindall, London), ERT had become available, but SRT and pharmacological chaperones were not available as potential therapies, and the focus of the book was more on clinical aspects than on basic science. In contrast, the current book includes a number of chapters dealing with molecular biology, crystallography, cell biology, and animal models, and includes new and updated chapters about various clinical and diagnostic features, as well as new chapters on novel therapeutic approaches other than ERT, including SRT and chaperone therapy. It is fair to say that much greater progress has been made in the 23 years between 1982 and 2005 than was made during the 100 years between 1882 and 1982, reflecting the exponential advances of science and biotechnology during the recent period.

Another innovative feature of this book is the inclusion of a section on the ethical, societal, and medical considerations associated with Gaucher disease as a model for LSDs and orphan diseases in general, with chapters written by patient organizations, pharmaceutical companies, physicians, public health leaders, and ethicists. We believe that the inclusion of this section significantly adds to the relevance and importance of this book.

Finally, it has been a challenge to write an up-to-date book on Gaucher disease. We believe that we have covered the most recent advances and apologize if something has been inadvertently left out. We would like to thank all of the authors of chapters for their excellent contributions, Jessica Futerman for help with editing, and Israela Tishler for help with formatting. We trust that the current book will be of use to basic scientists, to clinicians, to pharmaceutical companies looking for new areas of research with therapeutic potential, and perhaps of most importance, to patients and their families who are seeking to understand more about the disease with which they have been afflicted.