Neutralizing Antibodies Against Adeno-Associated Viral Capsids in Patients with mut Methylmalonic Acidemia

Human Gene Therapy
Elizabeth A HarringtonCharles P Venditti

Abstract

Isolated methylmalonic acidemia (MMA), a group of autosomal recessive inborn errors of metabolism, is most commonly caused by complete (mut(0)) or partial (mut(-)) deficiency of the enzyme methylmalonyl-CoA mutase (MUT). The severe metabolic instability and increased mortality experienced by many affected individuals, especially those with mut(0) MMA, has led centers to use elective liver transplantation as a treatment for these patients. We have previously demonstrated the efficacy of systemic adeno-associated viral (AAV) gene delivery as a treatment for MMA in a murine model and therefore sought to survey AAV antibody titers against serotypes 2, 8, and 9 in a group of well-characterized MMA patients, accrued via a dedicated natural history study ( clinicaltrials.gov ID: NCT00078078). Plasma samples provided by 42 patients (8 mut(-) and 34 mut(0); 10 had received organ transplantation), who ranged in age between 2 and 31 years, were analyzed to examine AAV2 (n = 35), AAV8 (n = 41), and AAV9 (n = 42) antibody titers. In total, the seroprevalence of antibodies against AAV2, AAV8, or AAV9 was 20%, 22%, and 24%, respectively. We observed a lower-than-expected seropositivity rate (titers ≥1:20) in the pediatric MMA patients (2-18 y...Continue Reading

Associated Clinical Trials

References

Apr 1, 1992·Journal of Paediatrics and Child Health·S N WongM Y Chan
Oct 1, 1967·Archives of Disease in Childhood·V G OberholzerW F Young
Apr 14, 1983·The New England Journal of Medicine·S M MatsuiL E Rosenberg
Jan 1, 1984·Journal of Inherited Metabolic Disease·J A ChurchG N Donnell
Jun 17, 1998·The Journal of Pediatrics·W G van 't HoffJ V Leonard
Aug 23, 2002·Proceedings of the National Academy of Sciences of the United States of America·Guang-Ping GaoJames M Wilson
Sep 18, 2002·Pediatric Transplantation·Liise K KaylerJohn C Magee
May 20, 2005·Journal of Inherited Metabolic Disease·S NagarajanM M Sarwal
Oct 11, 2005·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Daisuke MoriokaKoichi Tanaka
Jun 29, 2007·Pediatric Research·Friederike HörsterE Regula Baumgartner
Oct 3, 2007·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D MoriokaA Nakagawa
Oct 17, 2007·BMC Medical Genetics·Randy J ChandlerCharles P Venditti
Apr 17, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Carmela ZincarelliJoseph E Rabinowitz
Jan 13, 2009·The Journal of Infectious Diseases·Roberto CalcedoJames M Wilson
Apr 21, 2009·Molecular Genetics and Metabolism·M A CossonP de Lonlay
Oct 29, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lili WangJames M Wilson
Oct 29, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Randy J Chandler, Charles P Venditti
Nov 6, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Lili WangJames M Wilson
Jan 20, 2011·Molecular Therapy : the Journal of the American Society of Gene Therapy·Amit C NathwaniAndrew M Davidoff
Jul 22, 2011·Clinical and Vaccine Immunology : CVI·Roberto CalcedoJames M Wilson
Dec 14, 2011·The New England Journal of Medicine·Amit C NathwaniAndrew M Davidoff
Oct 24, 2013·Frontiers in Immunology·Roberto Calcedo, James M Wilson
Jun 25, 2014·Bioanalysis·Jenny HendriksStefan Kostense
Jun 25, 2014·Bioanalysis·Lydia MichautFabienne Deckert-Salva
Jan 22, 2015·The Journal of Clinical Investigation·Randy J ChandlerCharles P Venditti

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Citations

Jun 18, 2016·Human Gene Therapy. Clinical Development·Roberto Calcedo, James M Wilson
Nov 3, 2016·Current Opinion in Pediatrics·Jamie L Fraser, Charles P Venditti
Jun 5, 2018·Intractable & Rare Diseases Research·Xiaoyan ZhouJinxiang Han
Jul 16, 2019·Human Gene Therapy·Randy J Chandler, Charles P Venditti
Jun 9, 2020·Journal of Inherited Metabolic Disease·Hidde A ZittersteijnRob C Hoeben
May 24, 2019·Journal of Inherited Metabolic Disease·Hanneke A HaijesNanda M Verhoeven-Duif
Nov 2, 2017·The New England Journal of Medicine·Jerry R MendellBrian K Kaspar
Feb 6, 2020·BMC Medical Genetics·Parham HabibzadehMohammad Ali Faghihi
Mar 28, 2019·Nature Reviews. Neurology·Moacir Wajner
Dec 17, 2021·Systems Biology in Reproductive Medicine·Bin HeShuai Zhen

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Methods Mentioned

BETA
transfection

Clinical Trials Mentioned

NCT00078078

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