DEVELOPMENT OF AN RNA INTERFERENCE-BASED SYSTEM FOR THE MOLECULAR CELL THERAPY OF MYOTONIC DYSTROPHY

Myotonic dystrophy (DM), the most common form of adult muscular dystrophy, is primarily a muscle disorder but also affects other organs including the heart, eye, testes, lungs and brain. The disease is inherited with an autosomal dominant transmission and two different genetic mutations have been recognized so far as the primary molecular defect underlying this disorder. A singular feature is shared by these two mutations, which is the abnormal expansion of a trinucleotide (DM1) or tetranucleotide (DM2) repeat in untranslated regions of two different genes. It is currently hypothesized that this type of defect, although affecting apparently unrelated genes, can lead to similar clinical manifestations by interfering with the synthesis of other proteins. Although a considerable scientific effort has been performed about the precise pathogenic mechanisms of DM, no experimental therapeutic protocols have been developed. It is the purpose of this project to contribute to set up novel therapeutic strategies based on antisense RNA technology.