Prevalence of Anti-Adeno-Associated Virus Serotype 9 Antibodies in Adult Patients with Spinal Muscular Atrophy

Publikation: Beitrag in FachzeitschriftForschungsartikelBeigetragenBegutachtung


  • Benjamin Stolte - , LVR-Universitätsklinik Essen (Autor:in)
  • Olivia Schreiber-Katz - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • René Günther - , Klinik und Poliklinik für Neurologie, Deutsches Zentrum für Neurodegenerative Erkrankungen, Standort Dresden (Partner: DZNE der Helmholtzgemeinschaft), Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Claudia Diana Wurster - , Universitätsklinikum Ulm (Autor:in)
  • Susanne Petri - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Alma Osmanovic - , Medizinische Hochschule Hannover (MHH) (Autor:in)
  • Maren Freigang - , Klinik und Poliklinik für Neurologie, Universitätsklinikum Carl Gustav Carus Dresden (Autor:in)
  • Zeljko Uzelac - , Universitätsklinikum Ulm (Autor:in)
  • Markus Leo - , LVR-Universitätsklinik Essen (Autor:in)
  • Otgonzul von Velsen - , LVR-Universitätsklinik Essen (Autor:in)
  • Wibke Bayer - , LVR-Universitätsklinik Essen (Autor:in)
  • Ulf Dittmer - , LVR-Universitätsklinik Essen (Autor:in)
  • Christoph Kleinschnitz - , LVR-Universitätsklinik Essen (Autor:in)
  • Tim Hagenacker - , LVR-Universitätsklinik Essen (Autor:in)


5q-associated spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder that leads to progressive muscle atrophy and weakness. The disease is caused by a homozygous deletion or mutation in the survival of motor neuron 1 (SMN1) gene, resulting in insufficient levels of SMN protein. Onasemnogene abeparvovec-xioi (OA) is a nonreplicating vector based on adeno-associated virus serotype 9 (AAV9) that contains the full-length human SMN1 gene. Recently, OA was approved for the treatment of SMA by the U.S. Food and Drug Administration and the European Medicines Agency. Because the presence of neutralizing antibodies caused by previous natural exposure to wild-type adeno-associated viruses (AAVs) may impair the efficiency of AAV-mediated gene transfer and thus reduce the therapeutic benefit of the gene therapy, an AAV9-binding antibody titer of >1:50 was defined as a surrogate exclusion criterion in pivotal OA clinical trials. However, these studies were exclusively conducted in infants and children. Because data on anti-AAV9 antibody titers in adults are generally sparse and not available for adult patients with SMA, we determined the prevalence of anti-AAV9 antibodies in sera of adult individuals with SMA to evaluate the feasibility of AAV9-mediated gene therapy in this cohort. In our study population of 69 adult patients with SMA type 2 and type 3 from four German academic sites, only 3 patients (4.3%) had an elevated anti-AAV9 antibody titer of >1:50. The prevalence of anti-AAV9 antibodies did not increase with age. The low and age-independent prevalence of anti-AAV9 antibodies in our cohort provides evidence that gene therapy with intravenous administered recombinant AAV9 vectors (rAAV9) might be feasible in adult patients with SMA, regardless of the patients' sex, SMA type, walking ability, or ventilatory status. This could also apply to the treatment of other inherited neurological diseases with rAAV9.


Seiten (von - bis)968-976
FachzeitschriftHuman gene therapy
PublikationsstatusVeröffentlicht - Sept. 2022

Externe IDs

Scopus 85138457507


Ziele für nachhaltige Entwicklung


  • Antibodies, Neutralizing/genetics, Child, Dependovirus/genetics, Homozygote, Humans, Infant, Muscular Atrophy, Spinal/genetics, Prevalence, Sequence Deletion, Serogroup