24 Gene Therapy for Metabolic Inherited Diseases in Dogs

Abstract

Most of the genetic diseases for which gene therapy is a good candidate for potential therapy are considered rare disorders, and gene transfer is still a somewhat uncertain proposition in terms of safety, as has been borne out by recent human trials (Hacein-Bey-Abina et al. 2003; Raper et al. 2003). Driven by the need for safety, and the paucity of patients for many of these disorders, and with the potential difficulty of conducting studies with statistically meaningful outcomes, evaluating potential gene transfer protocols in animal models is an essential preliminary step. Although mouse models are the most practical for initial assessments, larger animal models are needed because mouse models may fail to faithfully mirror the human disease (Phaneuf et al. 1996; Ohshima et al. 1997), or because the larger animal models are superior for preclinical work, as their size is closer to that of humans, and they are longer-lived and less inbred, as are humans.

The benefits of using large animal models represent an important step in the preclinical evaluation of human-directed gene transfer protocols. For practical reasons, large animals have usually been limited to dogs and cats. Although some larger species, including ovine, porcine, caprine, and bovine, have been used in the past to better understand genetic diseases, considerations of size, housing, and reproduction have limited their use in treatment protocols. Dogs are particularly well represented as models for genetic diseases, because the wide diversity of breeds and breeding practices has led to a large number of distinct and...