Ganglioside Storage Diseases: On the Road to Management

Abstract

Although the biochemical and genetic basis for the GM1 and GM2 gangliosidoses has been known for decades, effective therapies for these diseases remain in early stages of development. The difficulty with many therapeutic strategies for treating the gangliosidoses comes largely from their inability to remove stored ganglioside once it accumulates in central nervous system (CNS) neurons and glia. This chapter highlights advances made using substrate reduction therapy and gene therapy in reducing CNS ganglioside storage. Information obtained from mouse and feline models provides insight on therapeutic strategies that could be effective in human clinical trials. In addition, information is presented showing how a calorie-restricted diet might facilitate therapeutic drug delivery to the CNS. The development of multiple new therapeutic approaches offers hope that longer-term management of these diseases can be achieved. It is also clear that multiple therapeutic strategies will likely be needed to provide the most complete management.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation

“…Using this paradigm, alterations in fundamental cellular behaviors, proliferation and neuronal differentiation, were identified, which raise the possibility that they could impact fetal brain development in GM2 gangliosidosis patients. While perhaps not contributing to acute neurodegeneration, they may be consequential when treatments are eventually devised to reverse enzyme deficiencies postnatally ( 70 – 72 ).…”