Carbohydrate-based therapeutics for lysosomal storage disorders

Chapter 9, Carbohydrate-Based Therapeutics for Lysosomal Storage Disorders (Chapter title) Lysosomal Storage Diseases (LSDs) are a group of metabolic disorders caused by loss‐of‐function mutations in lysosomal enzyme‐encoding genes, which leads to accumulation of unmetabolized substrates in the lysosomes, cell disfunction and consequent severe symptoms. The currently most employed treatments for LSDs, namely the Enzyme Replacement Therapy (ERT), the Substrate Reduction Therapy and the innovative Pharmacological Chaperone Therapy (PCT), all employ carbohydrate‐ based compounds in their preparation or as the active ingredient. This chapter collects the most relevant in vitro, pre‐clinical, and clinical studies conducted essentially on iminosugars (sugar mimics with a nitrogen atom replacing the endocyclic oxygen), with the aim of developing therapeutics for LSDs. The countless options for the design and preparations of PCs, together with the early stage understanding of their mechanism of action, makes the investigation of PCs for the treatment of LSDs the main topic of the chapter. The account is organized accordingly to LSDs classification into Mucopolysaccharidoses, Sphingolipidoses, Glycogen Storage Disorders, and Glycoproteinoses. For each disorder, the structure and the biological activity of the most relevant compounds are reported and commented.