title: [Lysosomal storage diseases: functional classification and treatment principles].
abstract: Until recently, lysosomes were only considered as the place of macromolecules degradation. To date, these organelles are considered as playing a key role in cellular homeostasis. The knowledge of their complex role allows a better understanding of the physiopathology of the diseases resulting from their dysfunction. Biosynthesis of lysosomal enzymes and routes for macromolecules influx within lysosomes are briefly described and a functional classification of lysosomal diseases, which allows a comprehensive approach of treatment rationale, is proposed. Except cystinosis which is a lysosomal membrane transport disorder the majority of current treatments aim at treating enzymatic defects. Normal enzyme can be brought by hoematopoietic cell transplant (or other cell therapies) or by infusions of human recombinant enzyme. The normal enzyme can be also produced in situ by bringing the normal gene: it is the objective of gene therapy The other therapeutic approaches aim at decreasing the quantity of non degraded substrate reaching the lysosomes by limiting its biosynthesis or thanks to small pharmacologic molecules, at increasing the residual enzyme activity by stabilizing the protein (chaperones) or by improving read through possibilities of some stop codons in special contexts. The better knowledge of secondary phenomena set by the cell in order to try to restore homeostasis which are sometimes more deleterious than the storage itself should allow to develop complementary treatments. The rationale of these different therapeutic approaches and their limits are described in this paper
authors.affiliation: Centre de Référence des Maladies Héréditaires du Métabolisme de Lyon, Hospices Civils de Lyon Hôpital Debrousse, 29, rue Soeur-Bouvier, 69322, Lyon, France. irene.maire@chu-lyon.fr
authors.forename: Irène
authors.initials: I
authors.lastname: Maire
mesh_terms: D057487:Enzyme Therapy; D006801:Humans; D016464:Lysosomal Storage Diseases / Q000145:classification / Q000628:therapy*; D004798:Enzymes
chemical_list: D004798:Enzymes