PMID- 17924344
OWN - NLM
STAT- MEDLINE
DCOM- 20071127
LR  - 20240414
IS  - 0002-9297 (Print)
IS  - 1537-6605 (Electronic)
IS  - 0002-9297 (Linking)
VI  - 81
IP  - 5
DP  - 2007 Nov
TI  - Enhanced response to enzyme replacement therapy in Pompe disease after the 
      induction of immune tolerance.
PG  - 1042-9
AB  - Pompe disease, which results from mutations in the gene encoding the 
      glycogen-degrading lysosomal enzyme acid alpha -glucosidase (GAA) (also called 
      "acid maltase"), causes death in early childhood related to glycogen accumulation 
      in striated muscle and an accompanying infantile-onset cardiomyopathy. The 
      efficacy of enzyme replacement therapy (ERT) with recombinant human GAA was 
      demonstrated during clinical trials that prolonged subjects' overall survival, 
      prolonged ventilator-free survival, and also improved cardiomyopathy, which led 
      to broad-label approval by the U.S. Food and Drug Administration. Patients who 
      lack any residual GAA expression and are deemed negative for cross-reacting 
      immunologic material (CRIM) have a poor response to ERT. We previously showed 
      that gene therapy with an adeno-associated virus (AAV) vector containing a 
      liver-specific promoter elevated the GAA activity in plasma and prevented 
      anti-GAA antibody formation in immunocompetent GAA-knockout mice for 18 wk, 
      predicting that liver-specific expression of human GAA with the AAV vector would 
      induce immune tolerance and enhance the efficacy of ERT. In this study, a very 
      low number of AAV vector particles was administered before initiation of ERT, to 
      prevent the antibody response in GAA-knockout mice. A robust antibody response 
      was provoked in naive GAA-knockout mice by 6 wk after a challenge with human GAA 
      and Freund's adjuvant; in contrast, administration of the AAV vector before the 
      GAA challenge prevented the antibody response. Most compellingly, the antibody 
      response was prevented by AAV vector administration during the 12 wk of ERT, and 
      the efficacy of ERT was thereby enhanced. Thus, AAV vector-mediated gene therapy 
      induced a tolerance to introduced GAA, and this strategy could enhance the 
      efficacy of ERT in CRIM-negative patients with Pompe disease and in patients with 
      other lysosomal storage diseases.
FAU - Sun, Baodong
AU  - Sun B
AD  - Division of Medical Genetics, Department of Pediatrics, Duke University Medical 
      Center, Durham, NC 27710, USA.
FAU - Bird, Andrew
AU  - Bird A
FAU - Young, Sarah P
AU  - Young SP
FAU - Kishnani, Priya S
AU  - Kishnani PS
FAU - Chen, Y-T
AU  - Chen YT
FAU - Koeberl, Dwight D
AU  - Koeberl DD
LA  - eng
GR  - R01 HL081122/HL/NHLBI NIH HHS/United States
GR  - R01 HL081122-01A1/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070921
PL  - United States
TA  - Am J Hum Genet
JT  - American journal of human genetics
JID - 0370475
RN  - 0 (Antibodies)
RN  - 0 (Recombinant Proteins)
RN  - 9005-79-2 (Glycogen)
RN  - EC 3.2.1.20 (GAA protein, human)
RN  - EC 3.2.1.20 (alpha-Glucosidases)
SB  - IM
MH  - Animals
MH  - Antibodies/pharmacology
MH  - Blotting, Western
MH  - Cell Line
MH  - Dependovirus/drug effects
MH  - Endpoint Determination
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Glycogen/metabolism
MH  - Glycogen Storage Disease Type II/*immunology/*therapy
MH  - Humans
MH  - Immune Tolerance/drug effects/*immunology
MH  - Mice
MH  - Muscle, Skeletal/cytology/drug effects
MH  - Myocardium/enzymology
MH  - Recombinant Proteins/administration & dosage/pharmacology
MH  - alpha-Glucosidases/administration & dosage/*immunology/pharmacology
PMC - PMC2265658
EDAT- 2007/10/10 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/05/01
CRDT- 2007/10/10 09:00
PHST- 2007/05/17 00:00 [received]
PHST- 2007/07/27 00:00 [accepted]
PHST- 2007/10/10 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/10/10 09:00 [entrez]
PHST- 2008/05/01 00:00 [pmc-release]
AID - S0002-9297(07)63878-6 [pii]
AID - 44973 [pii]
AID - 10.1086/522236 [doi]
PST - ppublish
SO  - Am J Hum Genet. 2007 Nov;81(5):1042-9. doi: 10.1086/522236. Epub 2007 Sep 21.