title: [Therapy of lysosomal storage diseases: update and perspectives].
abstract: Lysosomal storage diseases (LSD) are caused by monogenic mutations in genes coding for multiple aberrant proteins involved in the catabolism of complex lipids, glycosaminoglycans, oligosaccharides, or nucleic acids. The pathophysiology of the LSD is due to abnormal accumulation of non-hydrolyzed substrate in the lysosomes, affecting the architecture and function of cells, tissues and organs. Due to their genic and allelic heterogeneity the LSD present a wide clinical spectrum in severity of symptoms, evolution and age of onset. The therapeutic strategy has two goals: 1) Palliative management of symptoms (splenectomy, surgery to improve or restore joints or bones, drugs for CNS symptoms, etc.), and 2) The correction of activity of the mutant protein, the former has two approaches: A) Replacing deficient protein (bone marrow transplantation, hematopoietic stem cells or umbilical cord blood cells; replacement with recombinant enzyme and gene therapy) and B) Activate or enhanced the functionality of the mutant enzyme with therapeutic small molecules. Neither of the known treatments is able to address all aspects of these multisystemic disorders, nor cure the patients. Currently, the combination of corrective therapy (CT) with paliative therapy (PT) is the most promising strategy to solve most of the multisystem manifestations. The multidisciplinary medical care is fundamental for diagnosis, treatment and control of disease. Nanotechnology opens a promising new era in the treatment of LSD. Finally, the LSD that has CT must be included in newborn screening programs in order to implement timely treatment and prevent irreversible damage.
authors: Division de Genética, Centro de Investigación Biomédica de Occidente, Instituto Mexicano del Seguro Social de Jalisco. qfbrichar@yahoo.com.mx
authors: Ricardo Alejandro
authors: RA
authors: Lara-Aguilar
authors: Clara Ibet
authors: CI
authors: Juárez-Vázquez
authors: Claudina
authors: C
authors: Medina-Lozano
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019468:Disease Management; D056947:Enzyme Replacement Therapy; D015316:Genetic Therapy; D006801:Humans; D007231:Infant, Newborn; D016464:Lysosomal Storage Diseases / Q000175:diagnosis / Q000178:diet therapy / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D018832:Molecular Chaperones / Q000627:therapeutic use; D015997:Neonatal Screening; D010166:Palliative Care; D010348:Patient Care Team; D010443:Peptide Chain Termination, Translational / Q000187:drug effects; D017510:Protein Folding / Q000187:drug effects; D011994:Recombinant Proteins / Q000627:therapeutic use; D013156:Splenectomy; D033581:Stem Cell Transplantation
chemical_list: D000617:Aminoglycosides; D018832:Molecular Chaperones; D011994:Recombinant Proteins