Models to study basic and applied aspects of lysosomal storage disorders

Abstract

The lack of available treatments and fatal outcome in most lysosomal storage disorders (LSDs) have spurred research on pathological mechanisms and novel therapies in recent years. In this effort, experimental methodology in cellular and animal models have been developed, with aims to address major challenges in many LSDs such as patient-to-patient variability and brain condition. These techniques and models have advanced knowledge not only of LSDs but also for other lysosomal disorders and have provided fundamental insights into the biological roles of lysosomes. They can also serve to assess the efficacy of classical therapies and modern drug delivery systems. Here, we summarize the techniques and models used in LSD research, which include both established and recently developed in vitro methods, with general utility or specifically addressing lysosomal features. We also review animal models of LSDs together with cutting-edge technology that may reduce the need for animals in the study of these devastating diseases.

Keywords: Animal models; BBB; Lysosomes; Omics; Optogenetics; Organoids; Storage disorders; iPSCs.