[Therapeutic targets in Gaucher's disease].
Gaucher's disease (GD) occurs because of deficiency of the enzyme beta-glucocerebrosidase that results in accumulation of this glycolipid compound in the cells of the macrophage-monocyte system. There are 3 types: type 1 is non-neuronopathic with primarily visceral signs and symptoms which range tremendously in severity; infantile-onset type 2 and later-onset type 3 involve the central nervous system. More than 300 mutations have been described in the gene, partially explaining phenotypic heterogeneity. Commercialization in 1991 of the first enzyme replacement therapy, alglucerase, resulted in a revolution in the management of patients with symptomatic GD (i.e., by improving the hematological and visceral signs and symptoms). Within the first 5 years of alglucerase, its safety and efficacy in improving hemoglobin levels and platelet counts, and in reducing splenic and hepatic enlargement were confirmed albeit recognizing its inability to impact neurological symptoms and signs because of its large molecular size. Recombinant imiglucerase soon replaced alglucerase as the standard of care for GD. The therapeutic targets recently defined as treatment goals were: normalization of cell counts; reduction of liver and spleen volume; elimination of the infiltration in the bone marrow to prevent the complications, and improvement in surrogate biomarkers.
Grupo de Estudio de Enfermedad de Gaucher y Neoplasias Hematológicas, Servicio de Hematología, Hospital Universitario Miguel Servet, Centro de Investigación Biomédica en Red de Enfermedades Raras, Instituto Aragonés de Ciencias de la Salud, Zaragoza, Spain. giraldo.p@gmail.com
Pilar
P
Giraldo
Mercedes
M
Roca
D056947:Enzyme Replacement Therapy; D005776:Gaucher Disease / Q000097:blood / Q000188:drug therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006441:Hemoglobin A / Q000378:metabolism; D006529:Hepatomegaly / Q000188:drug therapy; D006801:Humans; D010976:Platelet Count; D013163:Splenomegaly / Q000188:drug therapy
C070292:alglucerase; D006441:Hemoglobin A; D005962:Glucosylceramidase; C090568:imiglucerase