Resumen

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 joint mobility or bones, drugs for CNS symptoms, etc.), and 2) The correction in 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 enhance the functionality of the mutant enzyme with therapeutic small molecules. Neither of the known treatment is able to address all aspects of these multisystemic disorders, nor cure the patients. Currently, the combination of corrective therapy (CT) with palliative 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.

Palabras clave: Storage lysosome chaperone therapy enzyme replacement therapy gene therapy substrate reduction therapy stem cells transplantation therapy.

2014-11-07   |   353 visitas   |   Evalua este artículo 0 valoraciones

Vol. 63 Núm.6. Noviembre-Diciembre 2011 Pags. 651-658 Rev Invest Clin 2011; 63(6-ENGLISH)