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

作者：Benjamin Stolte, Olivia Schreiber‐Katz, René Günther, Claudia D. Wurster, Susanne Petri, Alma Osmanovic, Maren Freigang, Željko Uzelac, Markus Leo, Otgonzul von Velsen, Wibke Bayer, Ulf Dittmer, Christoph Kleinschnitz, Tim Hagenacker · 发表于：Human Gene Therapy · 年份：2022 · DOI：10.1089/hum.2022.054 · 被引用次数：14 · 研究领域：Neurogenetic and Muscular Disorders Research、Viral Infections and Immunology Research、Virus-based gene therapy research

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. ...