Cell-and Gene-based Therapeutic Approaches for Neurological Deficits in Mucopolysaccharidoses

Dao      Pan

Abstract

Mucopolysaccharidoses (MPS) are a group of lysosomal storage diseases that are resulted from abnormal accumulation of glycosaminoglycans. Among the progressive multi-organ abnormalities often associated with MPS diseases, the deterioration of central nervous system (CNS) is the most challenging manifestations to be tackled, due to the impermeability of the blood-brain-barrier (BBB). Evolved with recent development in stem cell biotechnology and gene therapy, several novel experimental approaches have been investigated in animal models. In this review, we will address different approaches attempting to bypass the BBB for neuropathic MPS treatment using cell- and gene-based therapies. Several neurological findings in CNS pathophysiology emerged with therapeutic investigation will also be discussed.

Keywords: Mucopolysaccharidoses, central nervous system, blood-brain-barrier, animal models, stem cells, gene therapy, abnormal accumulation of glycosaminoglycans, multi-organ abnormalities, deterioration of central nervous system, dysostosis multiplex, Hurler syndrome, enzyme trafficking, lysosomal enzyme release and reuptake, hematopoietic stem cell (HSC) transplantation