[Enzyme replacement therapy for mucopolysaccharidoses I, II and VI: recommendations from a group of Brazilian F experts].
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.
Giugliani
Roberto
R
Departamento de Genética, Universidade Federal do Rio Grande do Sul.
Federhen
Andressa
A
Muñoz Rojas
Maria Verónica
MV
Vieira
Taiane Alves
TA
Artigalás
Osvaldo
O
Pinto
Louise Lapagesse Carmargo
LL
Azevedo
Ana Cecília
AC
Acosta
Angelina Xavier
AX
Bomfim
Carmem
C
Lourenço
Charles Marques
CM
Kim
Chong Ae
CA
Horovitz
Dafne
D
Souza
Denize Bomfim
DB
Norato
Denise
D
Marinho
Diane
D
Palhares
Durval
D
Santos
Emerson Santana
ES
Ribeiro
Erlane
E
Valadares
Eugênia Ribeiro
ER
Guarany
Fábio
F
De Lucca
Gisele Rosone
GR
Pimentel
Helena
H
Souza
Isabel Neves de
IN
Corrêa Neto
Jordão
J
Fraga
José Carlos
JC
Góes
José Eduardo
JE
Cabral
José Maria
JM
Simeonato
José
J
Llerena
Juan Clinton
JC
Jardim
Laura Bannach
LB
Giuliani
Liane de Rosso
Lde R
Silva
Luiz Carlos Santana da
LC
Santos
Mara
M
Moreira
Maria Angela
MA
Kerstenetzky
Marcelo
M
Ribeiro
Márcia
M
Ruas
Nicole
N
Barrios
Patricia
P
Aranda
Paulo
P
Honjo
Rachel
R
Boy
Raquel
R
Costa
Ronaldo
R
Souza
Carolina Fishinger Moura de
CF
Alcântara
Flavio F
FF
Avilla
Sylvio Gilberto A
SG
Fagondes
Simone
S
Martins
Ana Maria
AM
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