title: [Enzyme replacement therapy of lysosomal storage diseases].
abstract: Extraction and purification of an acid β-glucosidase from human placenta (alglucerase) for the treatment of Gaucher disease, replaced a few years later by a recombinant enzyme (imiglucérase, Cerezyme(®)), has paved the way to the development of enzyme replacement therapies (ERT) for the treatment of lysosomal storage diseases (LSD) among which Fabry disease for which the long-term efficacy of the two currently available preparations (agalsidase alfa, Replagal(®) and Fabrazyme(®)) is still being investigated. Mucopolysaccharidosis (MPS) type I (Hurler and Scheie diseases), II (Hunter syndrome) and VI (Maroteaux-Lamy disease) also benefit from ERT using laronidase (Aldurazyme(®)), idursulfase (Elaprase(®)) and galsulfase (Naglazyme(®)), respectively. ERT reduces the hepatosplenomegaly and improves the physical and respiratory capacities of MPS patients with a globally acceptable safety profile although the possibility of infusion-associated should always be kept in mind. Alglucosidase alpha (Myozyme(®)) improves the cardiomyopathy and life expectancy of infants suffering from Pompe disease and is under evaluation for the treatment of the juvenile and adult forms of the disease. CNS involvement remains a major challenge for many LSD and innovative research and approaches are needed to address the fact that recombinant enzymes do not cross the blood-brain barrier and therefore are not expected to lead to any improvement in CNS damages, except if alternative routes such as intrathecal administration would be developed. Molecular chaperones (e.g. migalastat for Fabry disease) and inhibitors of glucosylceramide synthesis (e.g. eliglustat tartrate for Gaucher disease) are currently under investigation in various clinical trials.
authors.affiliation: Université de Versailles - St Quentin en Yvelines (UVSQ), 78035 Versailles, France. dominique.germain@rpc.aphp.fr
authors.forename: D P
authors.initials: DP
authors.lastname: Germain
authors.forename: C
authors.initials: C
authors.lastname: Boucly
authors.forename: R Y
authors.initials: RY
authors.lastname: Carlier
authors.forename: E
authors.initials: E
authors.lastname: Caudron
authors.forename: P
authors.initials: P
authors.lastname: Charlier
authors.forename: F
authors.initials: F
authors.lastname: Colas
authors.forename: F
authors.initials: F
authors.lastname: Jabbour
authors.forename: V
authors.initials: V
authors.lastname: Martinez
authors.forename: S
authors.initials: S
authors.lastname: Mokhtari
authors.forename: D
authors.initials: D
authors.lastname: Orlikowski
authors.forename: N
authors.initials: N
authors.lastname: Pellegrini
authors.forename: C
authors.initials: C
authors.lastname: Perronne
authors.forename: H
authors.initials: H
authors.lastname: Prigent
authors.forename: R
authors.initials: R
authors.lastname: Rubinsztajn
authors.forename: K
authors.initials: K
authors.lastname: Benistan
mesh_terms: D056947:Enzyme Replacement Therapy / Q000379:methods*; D000795:Fabry Disease / Q000188:drug therapy*; D006801:Humans; D006867:Hydrolases / Q000627:therapeutic use*; D007066:Iduronate Sulfatase / Q000627:therapeutic use; D007068:Iduronidase / Q000627:therapeutic use; D016464:Lysosomal Storage Diseases / Q000188:drug therapy*; D008059:Mucopolysaccharidosis I / Q000188:drug therapy; D016532:Mucopolysaccharidosis II / Q000188:drug therapy; D009087:Mucopolysaccharidosis VI / Q000188:drug therapy; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D000519:alpha-Galactosidase / Q000627:therapeutic use*; D000520:alpha-Glucosidases / Q000627:therapeutic use
chemical_list: D011994:Recombinant Proteins; D006867:Hydrolases; D020051:N-Acetylgalactosamine-4-Sulfatase; C508864:galsulfase; D007066:Iduronate Sulfatase; C517982:idursulfase; C509951:GAA protein, human; D000520:alpha-Glucosidases; D000519:alpha-Galactosidase; D007068:Iduronidase