NEURAL PROGENITOR-CELL ENGRAFTMENT CORRECTS LYSOSOMAL STORAGE THROUGHOUT THE MPS-VII MOUSE-BRAIN

MANY metabolic diseases affecting the central nervous system are refra ctory to treatment because the blood-brain barrier restricts entry of therapeutic molecules. It may be possible to deliver therapeutic gene products directly to the brain by transplantation of neural progenitor cells, which can integrate into the murine central nervous system in a cytoarchitecturally appropriate manner(1-7). We tested this approach in mucopolysaccharidosis VII (Sly disease), a lysosomal storage disor der of humans, dogs and mice caused by an inherited deficiency of beta -glucuronidase(8-10). Lysosomal accumulation of glycosaminoglycans occ urs in the brain and other tissues, causing a fatal progressive degene rative disorder, including mental retardation(11). Treatments are desi gned to provide a source of normal enzyme for uptake by diseased cells (12-20). We report here that by transplanting beta-glucuronidase-expre ssing neural progenitors into the cerebral ventricles of newborn mice, donor cells engrafted throughout the neuraxis. At maturity, donor-der ived cells were present as normal constituents of diverse brain region s. beta-Glucuronidase activity was expressed along the entire neuraxis , resulting in widespread correction of lysosomal storage in neurons a nd glia in affected mice.