Neuronopathic LSDs: Quest for Treatments Drives Research in Nanomedicine and Nanotechnology

Lysosomal storage diseases (LSDs) are due to mutations in genes coding for high molecular weight lysosomal enzymes, which result in a deficiency or complete loss of enzyme activity and the consequent storage of undegraded substrate within lysosomes. Therapeutic approaches capable of modifying the natural history of the disease are available today and many have already entered into clinical practice. Among these, enzyme replacement therapy (ERT) represents an approved key treatment for a number of LSDs. Unfortunately, none of the used therapeutic replacement enzymes have, so far, proved to be effectively able to reach the central nervous system (CNS) in significant amounts and arrest neurodegeneration. Thus, currently, only the peripheral disease can be treated with ERT while storage product continues to accumulate in the CNS, resulting in severe neurodegeneration and premature death in childhood for all neurologically affected patients. In recent years, scientific advances in nanotechnology have led to development of revolutionary approaches potentially capable to provide a solution to the still unmet problem of increasing drug delivery across the Blood Brain Barrier. In particular, the growing interest in the medical applications of nanotechnology has contributed to the advent of a new field of applied science named nanomedicine that offers promising strategies to overcome several of the current impediments and disadvantages of ERT. The combination of existing nanotechnology with already available enzymes can, in fact, significantly improve the enzyme delivery opening a promising new era in the treatment of LSDs. This chapter aims to review the most recent advancement in nanomedicine and nanotechnology presenting novel therapeutic approaches designed to address neuronopathic LSDs.

Keywords: Blood-brain barrier, Enzyme replacement, Lysosomal storage diseases, Neurodegeneration, Nanomedicine, Nanotechnology.