Remyelination: cellular and gene therapy

Abstract

Dysfunctional myelination or oligodendroglial abnormalities play a prominent role in a vast array of pediatric neurological diseases of genetic, inflammatory, immunological, traumatic, ischemic, developmental, metabolic, and infectious causes. Recent advances in glial cell biology have suggested that effective remyelination strategies may, indeed, be feasible. Evidence for myelin repair is accumulating in various experimental models of dysmyelinating and demyelinating disease. Attempts at remyelination have either been directed towards creating myelin de novo from exogenous sources of myelin-elaborating cells or promoting an intrinsic spontaneous remyelinating process. Ultimately, some disorders of myelin may require multiple repair strategies, not only the replacement of dysfunctional cells (oligodendroglia) but also the delivery or supplementation of gene products (i.e., growth factors, immune modulators, metabolic enzymes). Although primary oligodendrocytes or oligodendroglial precursors may be effective for glial cell replacement in certain discrete regions and circumstances and although various genetic vectors may be effective for the delivery of therapeutic molecules, multipotent neural stem cells may be most ideally suited for both gene transfer and cell replacement on transplantation into multiple regions of the central nervous system under a wide range of pathological conditions. We propose that, by virtue of their inherent biological properties, neural stem cells possess the multifaceted therapeutic capabilities that many diseases characterized by myelin dysfunction in the pediatric population may demand.