Treatment of Neurological Manifestations of Mucopolysaccharidoses: Translational Considerations in Drug Development

Abstract

Since the development of Ceredase ® and Cerezyme ® for the treatment of Gaucher disease in the early 1990s, treatment of lysosomal storage disorders via enzyme replacement therapy (ERT) has provided life-changing benefit to patients and their families. Treating the neurological symptoms of these rare diseases, however, remains a significant unmet medical need. Here, we focus, as commentary on the recent publication by Grover et al, on the mucopolysaccharidosis (MPS) family of lysosomal storage diseases, in which one of enzymes required to break down the substrate of these enzymes, glycosaminoglycans (GAGs), are deficient [1]. In the absence of the enzyme, GAGs accumulate in systemic and central nervous system (CNS) tissues, leading to significant morbidity and mortality.The first direct approach is administration into the CSF, including via the intrathecal-lumbar, intrathecal-