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Type: Journal article
Title: Prevalence of anti-adeno-associated virus serotype 8 neutralizing antibodies and arylsulfatase B cross-reactive immunologic material in mucopolysaccharidosis VI patient candidates for a gene therapy trial
Author: Ferla, R.
Claudiani, P.
Savarese, M.
Kozarsky, K.
Parini, R.
Scarpa, M.
Donati, M.
Sorge, G.
Hopwood, J.
Parenti, G.
Fecarotta, S.
Nigro, V.
Sivri, H.
Van der Ploeg, A.
Andria, G.
Brunetti-Pierri, N.
Auricchio, A.
Citation: Human Gene Therapy, 2015; 26(3):145-152
Publisher: Mary Ann Liebert
Issue Date: 2015
ISSN: 1557-7422
Statement of
Rita Ferla, Pamela Claudiani, Marco Savarese, Karen Kozarsky, Rossella Parini, Maurizio Scarpa, Maria Alice Donati, Giovanni Sorge, John J. Hopwood, Giancarlo Parenti, Simona Fecarotta, Vincenzo Nigro, Hatice Serap Sivri, Ans Van Der Ploeg, Generoso Andria, Nicola Brunetti-Pierri, and Alberto Auricchio
Abstract: Recombinant vectors based on adeno-associated virus serotype 8 (AAV8) have been successfully used in the clinic and hold great promise for liver-directed gene therapy. Preexisting immunity against AAV8 or the development of antibodies against the therapeutic transgene product might negatively affect the outcomes of gene therapy. In the prospect of an AAV8-mediated, liver-directed gene therapy clinical trial for mucopolysaccharidosis VI (MPS VI), a lysosomal storage disorder caused by arylsulfatase B (ARSB) deficiency, we investigated in a multiethnic cohort of MPS VI patients the prevalence of neutralizing antibodies (Nab) to AAV8 and the presence of ARSB cross-reactive immunologic material (CRIM), which will either affect the efficacy of gene transfer or the duration of phenotypic correction. Thirty-six MPS VI subjects included in the study harbored 45 (62.5%) missense, 13 (18%) nonsense, 9 (12.5%) frameshift (2 insertions and 7 deletions), and 5 (7%) splicing ARSB mutations. The detection of ARSB protein in 24 patients out of 34 (71%) was predicted by the type of mutations. Preexisting Nab to AAV8 were undetectable in 19/33 (58%) analyzed patients. Twelve out of 31 patients (39%) tested were both negative for Nab to AAV8 and CRIM-positive. In conclusion, this study allows estimating the number of MPS VI patients eligible for a gene therapy trial by intravenous injections of AAV8.
Keywords: Humans; Dependovirus; Mucopolysaccharidosis VI; N-Acetylgalactosamine-4-Sulfatase; Cohort Studies; DNA Mutational Analysis; Cross Reactions; Mutation; Patient Selection; Turkey; Italy; Netherlands; Antibodies, Neutralizing; Genetic Therapy
Rights: © Rita Ferla et al. 2015; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons License Attribution-Non-Commercial Share Alike (
RMID: 0030031889
DOI: 10.1089/hum.2014.109
Appears in Collections:Medicine publications

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