Harnessing the potential of dystrophin-related proteins for ameliorating Duchenne's muscular dystrophy.

TY - JOUR

T1 - Harnessing the potential of dystrophin-related proteins for ameliorating Duchenne's muscular dystrophy.

AU - Krag, T O

AU - Gyrd-Hansen, M

AU - Khurana, T S

N1 - Keywords: Animals; Cats; Cytoskeletal Proteins; Disease Models, Animal; Dogs; Dystrophin; Gene Therapy; Humans; Membrane Proteins; Mice; Mice, Knockout; Muscular Dystrophy, Animal; Muscular Dystrophy, Duchenne; Up-Regulation; Utrophin

PY - 2001

Y1 - 2001

N2 - Duchenne's muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin-related proteins (DRPs): the chromosome 6-encoded DRP or utrophin, the chromosome-X encoded, DRP2 and the chromosome-18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin-deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin-deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin-deficient animal models.

AB - Duchenne's muscular dystrophy (DMD) is a fatal disease caused by mutations in the DMD gene that lead to quantitative and qualitative disturbances in dystrophin expression. Dystrophin is a member of the spectrin superfamily of proteins. Dystrophin itself is closely related to three proteins that constitute a family of dystrophin-related proteins (DRPs): the chromosome 6-encoded DRP or utrophin, the chromosome-X encoded, DRP2 and the chromosome-18 encoded, dystrobrevin. These proteins share sequence similarity and functional motifs with dystrophin. Current attempts at somatic gene therapy of DMD face numerous technical problems. An alternative strategy for DMD therapy, that circumvents many of these problems, has arisen from the demonstration that the DRP utrophin can functionally substitute for the missing dystrophin and its overexpression can rescue dystrophin-deficient muscle. Currently, a promising avenue of research consists of identifying molecules that would increase the expression of utrophin and the delivery of these molecules to dystrophin-deficient tissues as a means of DMD therapy. In this review, we will focus on DRPs from the perspective of strategies and issues related to upregulating utrophin expression for DMD therapy. Additionally, we will address the techniques used for anatomical, biochemical and physiological evaluation of the potential benefits of this and other forms of DMD therapy in dystrophin-deficient animal models.

M3 - Journal article

C2 - 11412148

SN - 1748-1708

VL - 171

SP - 349

EP - 358

JO - Acta Physiologica

JF - Acta Physiologica

IS - 3

ER -