Lysosomal Storage Disorders (LSDs), also known as lysosomal diseases (LDs) are a group of serious
genetic diseases characterized by not only the accumulation of non-catabolized compounds in the lysosomes due
to the deficiency of specific enzymes which usually eliminate these compounds, but also by trafficking, calcium
changes and acidification. LDs mainly affect the central nervous system (CNS), which is difficult to reach for
drugs and biological molecules due to the presence of the blood-brain barrier (BBB). While some therapies have
proven highly effective in treating peripheral disorders in LD patients, they fail to overcome the BBB.
Researchers have developed many strategies to circumvent this problem, for example, by creating carriers for
enzyme delivery, which improve the enzyme’s half-life and the overexpression of receptors and transporters in
the luminal or abluminal membranes of the BBB. This review aims to successfully examine the strategies developed
during the last decade for the treatment of LDs, which mainly affect the CNS. Among the LD treatments,
enzyme-replacement therapy (ERT) and gene therapy have proven effective, while nanoparticle, fusion protein,
and small molecule-based therapies seem to offer considerable promise to treat the CNS pathology. This work
also analyzed the challenges of the study to design new drug delivery systems for the effective treatment of LDs.
Polymeric nanoparticles and liposomes are explored from their technological point of view and for the most relevant
preclinical studies showing that they are excellent choices to protect active molecules and transport them
through the BBB to target specific brain substrates for the treatment of LDs.
Property of Lysosomal Storage Disease Associated with Midbrain Pathology in the Central Nervous System of Lamp-2–Deficient Mice