Adeno-associated virus (AAV) vector-based disease-modifying drugs could still be effective for patients with spinal muscular atrophy (SMA) once they reach adulthood, according to a study recently published in Human Gene Therapy.

“Because these antibodies can compromise vector-based gene transfer and the prevalence of anti-AAV antibodies generally increases with age, it is often assumed that there is a narrow window of opportunity for therapy that could exclude adult patients from treatment,” the authors explained.

This study included 69 patients aged 20 to 58 years (median, 34 years) who had been previously diagnosed with SMA type 2 or 3 with a confirmed homozygous deletion of exon 7, exon 8, or both. All participants underwent blood sampling to determine the levels of anti-AAV serotype 9 (AAV9) antibodies.

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Only 4.3% of patients, which accounts for 3 individuals in this sample, had an increased anti-AAV9 antibody titer above 1:50. Importantly, the researchers did not find an increase in antibody titer to be related to age.

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Moreover, the authors hypothesized that other demographic and clinical factors—such as sex, SMA subtype, and disease status, assessed by ventilatory function and walking capacity—would not showcase any relation with anti-AAV9 antibody plasma levels.

The relevance of these results lies in the concern that onasemnogene abeparvovec-xioi, a recently developed drug for SMA, would not be as useful to treat this disease since it depends on AAV9 as a vector and previous exposure to wild-type AAV9 could result in neutralizing antibodies.

Thus, past research determined that an anti-AAV9 antibody titer higher than 1:50 would be an exclusion criterion for patients to receive this therapy. Although these studies included only pediatric populations, the belief that anti-AAV9 antibodies increase with age compromised the use of this therapy in adults.

“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 patient’s sex, SMA type, walking ability, or ventilatory status,” the study authors concluded.


Stolte B, Schreiber-Katz O, Günther R, et al. Prevalence of anti-AAV9 antibodies in adult patients with spinal muscular atrophy. Hum Gene Ther. Published online August 9, 2022. doi:10.1089/hum.2022.054