ABSTRACT
Dystrophin is a member of the spectrin superfamily of proteins and is closely related to the three proteins that constitute the dystrophin-related protein family, including the autosomal homologue, utrophin. The potential of utrophin to functionally compensate for dystrophin has been directly demonstrated in experiments using transgene and viral vector driven utrophin overexpression to ameliorate the dystrophic phenotype in mdx muscle (1-6). Thus, one potential approach for therapy of Duchenne muscular dystrophy (DMD) is to increase utrophin levels in muscle by increasing the transcriptional expression via promoter activation. In this chapter, we summarize the data that illustrates utrophin can compensate for the lack of dystrophin in dystrophic muscle, and is thus a desirable target for DMD therapeutic design. We review progress in methodologies for gene delivery, understanding control of endogenous expression, and strategies
being utilized in the design and/or discovery of small pharmacological compounds for a utrophin-based upregulation strategy.
