PMID- 22909060
OWN - NLM
STAT- MEDLINE
DCOM- 20130605
LR  - 20220309
IS  - 1557-7422 (Electronic)
IS  - 1043-0342 (Linking)
VI  - 23
IP  - 12
DP  - 2012 Dec
TI  - Correction of pathological accumulation of glycosaminoglycans in central nervous 
      system and peripheral tissues of MPSIIIA mice through systemic AAV9 gene 
      transfer.
PG  - 1237-46
LID - 10.1089/hum.2012.029 [doi]
AB  - Mucopolysaccharidosis type IIIA (MPSIIIA) is a rare lysosomal storage disorder 
      caused by mutations in the sulfamidase gene. Accumulation of glycosaminoglycan 
      (GAG) inside the lysosomes is associated with severe neurodegeneration as well as 
      peripheral organ pathological changes leading to death of affected individuals 
      during adolescence. There is no cure for MPSIIIA. Due to the limitation of the 
      blood-brain barrier, enzyme replacement therapy and gene therapy strategies 
      attempted thus far have not achieved whole-body correction of the disease. After 
      the systemic administration of an adeno-associated virus 9 (AAV9) vector encoding 
      for sulfamidase under the control of a ubiquitous promoter, we were able to 
      obtain widespread expression of the therapeutic transgene in brain and in 
      peripheral organs, and sulfamidase activity in serum of both male and female 
      MPSIIIA mice. This was accompanied by the normalization of GAG storage levels in 
      most peripheral organs. In brain, decrease in GAG tissue content following AAV9 
      gene transfer of sulfamidase was associated with the resolution of 
      neuroinflammation. Finally, correction of disease phenotype resulted in a 
      remarkable prolongation of survival of both male and female AAV-treated MPSIIIA 
      mice. This proof-of-concept study will be relevant to the future development of 
      therapies for MPSIIIA.
FAU - Ruzo, Albert
AU  - Ruzo A
AD  - Center of Animal Biotechnology and Gene Therapy, Department of Biochemistry and 
      Molecular Biology, School of Veterinary Medicine, Universitat Autonoma de 
      Barcelona, 08193 Bellaterra, Spain.
FAU - Marco, Sara
AU  - Marco S
FAU - Garcia, Miquel
AU  - Garcia M
FAU - Villacampa, Pilar
AU  - Villacampa P
FAU - Ribera, Albert
AU  - Ribera A
FAU - Ayuso, Eduard
AU  - Ayuso E
FAU - Maggioni, Lucca
AU  - Maggioni L
FAU - Mingozzi, Federico
AU  - Mingozzi F
FAU - Haurigot, Virginia
AU  - Haurigot V
FAU - Bosch, Fatima
AU  - Bosch F
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121017
PL  - United States
TA  - Hum Gene Ther
JT  - Human gene therapy
JID - 9008950
RN  - 0 (Glycosaminoglycans)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.10.1.1 (N-sulfoglucosamine sulfohydrolase)
SB  - IM
MH  - Animals
MH  - Central Nervous System/metabolism
MH  - Dependovirus/genetics
MH  - Disease Models, Animal
MH  - Female
MH  - Gene Expression
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage/*pharmacology
MH  - Glycosaminoglycans/*metabolism
MH  - Hydrolases/*genetics
MH  - Liver/metabolism
MH  - Lysosomes/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mucopolysaccharidosis III/genetics/pathology/*therapy
MH  - Transgenes
EDAT- 2012/08/23 06:00
MHDA- 2013/06/06 06:00
CRDT- 2012/08/23 06:00
PHST- 2012/08/23 06:00 [entrez]
PHST- 2012/08/23 06:00 [pubmed]
PHST- 2013/06/06 06:00 [medline]
AID - 10.1089/hum.2012.029 [doi]
PST - ppublish
SO  - Hum Gene Ther. 2012 Dec;23(12):1237-46. doi: 10.1089/hum.2012.029. Epub 2012 Oct 
      17.