Lysosomal acid hydrolase

The term 'Lysosomal protein replacement' refers to a therapeutic class and platform rather than a specific molecular target. It encompasses a group of lysosomal acid hydrolases—such as glucocerebrosidase, alpha-galactosidase A, and acid alpha-glucosidase—that are deficient in patients with various lysosomal storage disorders (LSDs). These enzymes are essential for the breakdown of complex macromolecules including lipids, proteins, and glycans within the acidic environment of the lysosome. When these enzymes are missing or dysfunctional, substrates accumulate, leading to progressive cellular damage and multi-organ dysfunction. Modern pharmaceutical interventions utilize recombinant DNA technology to produce functional versions of these enzymes, which are then administered to patients to bypass the genetic defect. While highly effective for systemic symptoms, these therapies often face challenges in treating central nervous system symptoms due to their inability to cross the blood-brain barrier (Frontiers, 2020; MDPI, 2023).

Other names

Lysosomal enzymeLysosomal proteinEnzyme replacement therapy (ERT) targetLysosomal hydrolase

Enzyme replacement therapy involves the intravenous administration of a recombinant version of a deficient lysosomal enzyme; these exogenous proteins are typically internalized by target cells through receptor-mediated endocytosis (primarily via mannose-6-phosphate receptors) and subsequently trafficked to the lysosomal compartment where they restore the catabolic degradation of accumulated biological substrates (NCBI, 2013; PMC, 2021).