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Adeno-associated virus serotype 9 antibody titers in patients with SMA pre-screened for treatment with onasemnogene abeparvovec –routine care evidence

Gene Therapy volume 30, pages 101–106 (2023)Cite this article

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Abstract

Spinal muscular atrophy (SMA) is characterized by progressive weakness of skeletal and respiratory muscles. This study aimed to evaluate the prevalence of pre-existing anti adeno-associated virus serotype 9 antibody (AAV9-Ab) titers among infantile-onset SMA diagnosed infants pre-screened for treatment with AAV9-based onasemnogene abeparvovec, and to explore whether clinical and/or demographic characteristics are correlated with AAV9 Ab test results. This is a retrospective multicenter study of children diagnosed with 5q SMA younger than two years of age. The obtained data included demographic data, SMA type, SMN2 gene copy number, onset date, and results of AAV9-Ab test and of SMA prior treatments. Thirty-four patients were enrolled; six patients had positive results of AAV9-Ab (titer > 1:50) in the initial screening, 15 patients were re-tested for AAV9-Abs, of whom, three patients had seroreverted [1.5–4.5 months] between the two AAV9-Abs tests. One patient had seroconverted (5.5 months after the first AAV9-Abs test). The remaining 11 patients presented matching titer results in the two tests. No demographic/clinical factors were correlated to high AAV9-Abs titers (P > 0.05).We recommend AAV9-Ab re-tests to be performed until the age of 8 months, or, if 1.5 months or more have passed after the initial AAV9-Abs test.

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Fig. 1: Study flow chart of patients' inclusion.

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Anonymized data can be made available upon (reasonable) request.

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Acknowledgements

The authors thank, Fadwa Dabbah-Assadi, Ph.D. (Bioforum, Israel) for writing assistance. This research was funded by Novartis Gene Therapies Inc. (grant number PS2031) NGT had no involvement in conduct of the research, writing and submission.

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Authors and Affiliations

  1. Institute of Pediatric Neurology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel

    Sharon Aharoni, Jacob Bistritzer, Rony Cohen & Yoram Nevo

  2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Sharon Aharoni, Hagit Levine, Liora Sagi, Aviva Fattal-Valevski, Rony Cohen & Yoram Nevo

  3. Pediatric Neurology Unit, Soroka University Medical Center, Ben Gurion University, Beer Sheva, Israel

    Jacob Bistritzer & Iris Noyman

  4. Pulmonary Institute, Schneider Children’s Medical Center, Petach Tikva, Israel

    Hagit Levine

  5. Pediatric Neurology Institute, Dana-Dwek Children’s Hospital, Tel Aviv Medical Center, Tel Aviv, Israel

    Liora Sagi & Aviva Fattal-Valevski

  6. Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel

    Mira Ginzberg

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  1. Sharon Aharoni
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Contributions

SA: Drafting/revision of the manuscript for content, including medical writing for content; Major role in the acquisition of data; Study concept or design; Analysis or interpretation of data. JB: Drafting/revision of the manuscript for content Major role in the acquisition of data. HL: Drafting/revision of the manuscript for content, interpreted the results.LS: Acquired data, Drafting/revision of the manuscript for content. AFV: Drafting/revision of the manuscript for content, including medical writing for content and interpreted results.MG: Drafting/revision of the manuscript for content and acquired data.IN: Drafting/revision of the manuscript for content and acquired data. RC: Drafting/revision of the manuscript for content, interpreted the results. YN: Drafting/revision of the manuscript for content, including medical writing for content; Study concept or design; Analysis or interpretation of data.

Corresponding author

Correspondence to Sharon Aharoni.

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Competing interests

SA has received clinical trial funding from AveXis/Novartis Gene Therapies and Biogen and has served on scientific advisory boards for AveXis/Novartis Gene Therapies. All other authors declare no competing interests.

Ethical approval

The study was approved by the Institutional Review Boards of the four Medical Centers. All analyses were performed on anonymized data. The approval for the study was provided by the local ethics committees, including at the Schneider Medical Center (RMC-0519-20); Tel Aviv Medical Center (TLV-873-18), Wolfson Medical Center (WOMC-0053-21), and Soroka Medical Center (SOR-0109-21).

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Aharoni, S., Bistritzer, J., Levine, H. et al. Adeno-associated virus serotype 9 antibody titers in patients with SMA pre-screened for treatment with onasemnogene abeparvovec –routine care evidence. Gene Ther 30, 101–106 (2023). https://doi.org/10.1038/s41434-022-00339-0

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