Multiple Sclerosis (MS) is the prototypical CNS demyelinating disease, and though remyelination often occurs in the early stages of the disease, it eventually fails in later stages, contributing to progressive functional decline. All approved medical therapies for MS serve to suppress or modulate the activity of immune cells that are believed to play a role in the pathogenesis of the disease, but none are targeted specifically at preserving or repairing myelin. Therefore, the major goal of our laboratory, and the aim of the present proposal, is to gain newer understanding of the molecular mechanisms responsible for proliferation and remyelination with the expectation that this information will provide new therapeutic targets to protect myelin and enhance myelin repair in diseases such as MS. The specialized ends of chromosomes, or telomeres, protect eukaryotic organisms from DNA degradation, chromosomal fusion, and the activation of DNA repair mechanisms. Telomere maintenance in dividing cells requires the enzyme telomerase. The role that telomeres and telomerase play in regulating the proliferative capacity and differentiation of oligodendrocyte precursor cells (OPCs) is not well understood. This failure of remyelination in multiple sclerosis may be due, (a) in part to depletion of OPC pools resulting from successive rounds of demyelination and remyelination, (b) in part to insufficient activation of myelination by OPC. In this proposal, using transgenic animals, we ask the following questions, (1) how does the absence of telomerase affect myelination? and (2) How does the absence of telomerase affect remyelination?. The long-term goals of this study are to determine whether drugs targeted at telomerase can be used to enhance oligodendrocyte growth and remyelination, which might be useful in the treatment of MS.
Multiple sclerosis (MS) is the prototypical CNS demyelinating disease, and though remyelination often occurs in the early stages of the disease, it eventually fails in later stages, contributing to progressive functional decline. All approved medical therapies for MS serve to suppress or modulate the activity of immune cells that are believed to play a role in the pathogenesis of the disease, but none are targeted specifically at preserving or repairing myelin. Therefore, the major goal of our laboratory, and the aim of the present proposal, is to gain newer understanding of the molecular mechanisms responsible for proliferation and remyelination with the expectation that this information will provide new therapeutic targets to protect myelin and enhance myelin repair in diseases such as MS.
