Hyaluronan Oligosaccharides for the Promotion of Remyelination (Revised).

摘要

The overall goal of this project was to determine if digestion products of the glycosaminoglycan hyaluronan (HA) generated by hyaluronidases expressed by oligodendrocyte progenitor cells (OPCs) block OPC differentiation and remyelination; and if particular formulations of HA oligosaccharides could block the activities of these digestion products. During the course of this study, we determined that a specific hyaluronidase, PH20, is induced in OPCs and astrocytes in demyelinating lesions; that PH20 generates a unique profile of HA digestion products; that these products are sufficient to inhibit OPC maturation and remyelination; and that blocking PH20 activity can promote remyelination. These findings are now in press in Annals of Neurology and suggest a new drug target for the promotion of remyelination in multiple sclerosis and related demyelinating diseases.