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Lysosomal storage disorders (LSD) are a group of inherited diseases that result as a consequence of the loss of one or more of the several lysosomal enzymes that are responsible for the catabolism of a variety of macromolecules. The LSD as a group, present with an incidence of approximately 1 in 7500 live births making it one of the more prevalent groups of genetic diseases. The description of the pathophysiology of LSD, as well as their biochemical basis has facilitated the development of several therapeutic approaches for the treatment of this group of disorders. These include the use of enzyme replacement (see Chapter 3, this book), substrate inhibition (see Chapter 11, this book), and cell and gene-based therapies (see Chapter 14, this book). Enzyme and of these diseases. However, for a large number of the LSD, especially those affecting small molecule therapies have been successfully developed for a small number the central nervous system, no therapies are available as yet. Moreover, improvements to the current treatments are desirable and are under active consideration by a number of investigators. This review focuses specifically on the potential of gene therapy and in particular the use of recombinant adeno-associated viral (AAV) vectors as an alternate approach to treat the visceral and CNS manifestations shown associated with these enzymatic deficiencies. [ABSTRACT FROM AUTHOR]

The ability to mediate gene transfer to the lumen of the lung offers opportunities to treat diseases that affect the airways. Currently, several different gene-transfer vectors are being evaluated for delivery of a variety of therapeutic genes to the airways. These include recombinant viral (adenovirus, adeno-associated virus, retrovirus) and synthetic, self-assembling (cationic lipids, polymers) vectors. Although much of the early focus of these vectors has been directed toward a therapy for cystic fibrosis (1-5), other lung diseases, including asthma, chronic obstructive pulmonary disease, and cancer are being explored as viable disease targets. [ABSTRACT FROM AUTHOR]

Following the identification and subsequent cloning of the gene that is defective in patients with cystic fibrosis (CF), there has been a substantial effort to evaluate gene therapy as a modality for treating this disease. As the primary cause of mortality in CF is respiratory dysfunction, the lung has been the major focus for genetic therapy intervention. Although this organ is relatively accessible for gene transduction-for example, by use of aerosols-it has become evident that there are several barriers to efficient transduction of the airway epithelia. These barriers are often further exacerbated in a diseased CF lung. [ABSTRACT FROM AUTHOR]