title: [Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts].
abstract: Mucopolysaccharidoses (MPS) are rare genetic diseases caused by deficiency of specific lysosomal enzymes that affect catabolism of glycosaminoglycans (GAG). Accumulation of GAG in various organs and tissues in MPS patients results in a series of signs and symptoms, producing a multisystemic condition affecting bones and joints, the respiratory and cardiovascular systems and many other organs and tissues, including in some cases, cognitive performance. So far, eleven enzyme defects that cause seven different types of MPS have been identified. Before introduction of therapies to restore deficient enzyme activity, treatment of MPS focused primarily on prevention and care of complications, still a very important aspect in the management of these patients. In the 80's treatment of MPS with bone marrow transplantation/hematopoietic stem cells transplantation (BMT/HSCT) was proposed and in the 90's, enzyme replacement therapy (ERT),began to be developed and was approved for clinical use in MPS I, II and VI in the first decade of the 21st century. The authors of this paper are convinced that a better future for patients affected by mucopolysaccharidoses depends upon identifying, understanding and appropriately managing the multisystemic manifestations of these diseases. This includes the provision of support measures (which should be part of regular multidisciplinary care of these patients) and of specific therapies. Although inhibition of synthesis of GAG and the recovery of enzyme activity with small molecules also may play a role in the management of MPS, the breakthrough is the currently available intravenous ERT. ERT radically changed the setting for treatment of mucopolysaccharidosis I, II and VI in the last decade., Benefits can even be extended soon to MPS IV A (ERT for this condition is already in clinical development), with prediction for treatment of MPS III A and the cognitive deficit in MPS II by administration of the enzyme directly into the central nervous system (CNS). A large number of Brazilian services, from all regions of the country, already have experience with ERT for MPS I, II and VI. This experience was gained not only by treating patients but also with the participation of some groups in clinical trials involving ERT for these conditions. Summing up the three types of MPS, more than 250 patients have already been treated with ERT in Brazil. The experience of professionals coupled to the data available in international literature, allowed us to elaborate this document, produced with the goal of bringing together and harmonize the information available for the treatment of these severe and progressive diseases, which, fortunately, are now treatable, a situation which bring new perspectives for Brazilian patients, affected by these conditions.
authors.affiliation: Departamento de Genética, Universidade Federal do Rio Grande do Sul.
authors.forename: Roberto
authors.initials: R
authors.lastname: Giugliani
authors.forename: Andressa
authors.initials: A
authors.lastname: Federhen
authors.forename: Maria Verónica
authors.initials: MV
authors.lastname: Muñoz Rojas
authors.forename: Taiane Alves
authors.initials: TA
authors.lastname: Vieira
authors.forename: Osvaldo
authors.initials: O
authors.lastname: Artigalás
authors.forename: Louise Lapagesse Carmargo
authors.initials: LL
authors.lastname: Pinto
authors.forename: Ana Cecília
authors.initials: AC
authors.lastname: Azevedo
authors.forename: Angelina Xavier
authors.initials: AX
authors.lastname: Acosta
authors.forename: Carmem
authors.initials: C
authors.lastname: Bomfim
authors.forename: Charles Marques
authors.initials: CM
authors.lastname: Lourenço
authors.forename: Chong Ae
authors.initials: CA
authors.lastname: Kim
authors.forename: Dafne
authors.initials: D
authors.lastname: Horovitz
authors.forename: Denize Bomfim
authors.initials: DB
authors.lastname: Souza
authors.forename: Denise
authors.initials: D
authors.lastname: Norato
authors.forename: Diane
authors.initials: D
authors.lastname: Marinho
authors.forename: Durval
authors.initials: D
authors.lastname: Palhares
authors.forename: Emerson Santana
authors.initials: ES
authors.lastname: Santos
authors.forename: Erlane
authors.initials: E
authors.lastname: Ribeiro
authors.forename: Eugênia Ribeiro
authors.initials: ER
authors.lastname: Valadares
authors.forename: Fábio
authors.initials: F
authors.lastname: Guarany
authors.forename: Gisele Rosone
authors.initials: GR
authors.lastname: De Lucca
authors.forename: Helena
authors.initials: H
authors.lastname: Pimentel
authors.forename: Isabel Neves de
authors.initials: IN
authors.lastname: Souza
authors.forename: Jordão
authors.initials: J
authors.lastname: Corrêa Neto
authors.forename: José Carlos
authors.initials: JC
authors.lastname: Fraga
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Góes
authors.forename: José Maria
authors.initials: JM
authors.lastname: Cabral
authors.forename: José
authors.initials: J
authors.lastname: Simeonato
authors.forename: Juan Clinton
authors.initials: JC
authors.lastname: Llerena
authors.forename: Laura Bannach
authors.initials: LB
authors.lastname: Jardim
authors.forename: Liane de Rosso
authors.initials: Lde R
authors.lastname: Giuliani
authors.forename: Luiz Carlos Santana da
authors.initials: LC
authors.lastname: Silva
authors.forename: Mara
authors.initials: M
authors.lastname: Santos
authors.forename: Maria Angela
authors.initials: MA
authors.lastname: Moreira
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kerstenetzky
authors.forename: Márcia
authors.initials: M
authors.lastname: Ribeiro
authors.forename: Nicole
authors.initials: N
authors.lastname: Ruas
authors.forename: Patricia
authors.initials: P
authors.lastname: Barrios
authors.forename: Paulo
authors.initials: P
authors.lastname: Aranda
authors.forename: Rachel
authors.initials: R
authors.lastname: Honjo
authors.forename: Raquel
authors.initials: R
authors.lastname: Boy
authors.forename: Ronaldo
authors.initials: R
authors.lastname: Costa
authors.forename: Carolina Fishinger Moura de
authors.initials: CF
authors.lastname: Souza
authors.forename: Flavio F
authors.initials: FF
authors.lastname: Alcântara
authors.forename: Sylvio Gilberto A
authors.initials: SG
authors.lastname: Avilla
authors.forename: Simone
authors.initials: S
authors.lastname: Fagondes
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Martins
mesh_terms: D001938:Brazil; D056947:Enzyme Replacement Therapy / Q000379:methods* / Q000706:statistics & numerical data; D006801:Humans; D009083:Mucopolysaccharidoses / Q000145:classification / Q000188:drug therapy*; D017410:Practice Guidelines as Topic