Grant: Operating Grant

The aim of the project is to develop a new treatment for DMD based on the systemic delivery of a protein called laminin 111 alone or in combination with myoblast transplantation. The treatment would be applicable to all DMD patients independently of their mutation. Dystrophin normally links the contracting proteins with the muscle fiber membrane and in turn with the extracellular matrix proteins. These links ensures that the muscle fiber is not damage during contraction. In the absence of dystrophin, these links do not exist and thus the muscle fiber membrane is frequently damage during normal muscle activity. Laminin 111 is a matrix protein, which is normally present during embryogenesis but is absent in adult animals. It has recently been shown that the systemic delivery of this protein can restore the expression of alpha7beta1 integrin and make links between the membrane and the matrix. This protects the dystrophic muscle fiber during contraction. Moreover, laminin 111 has also been shown to increase the migration of myoblasts. Thus in this grant proposal we will investigate whether laminin 111 can by itself slow down the progression of the dystrophy, can improve the transplantation of myoblasts and whether laminin 111 could be delivered permanently by genetically modified myoblasts.