Objective: Onasemnogene abeparvovec (OA) is an AAV9-based gene therapy for spinal muscular atrophy type I (SMA I). Real-world outcomes show increased response variability compared to clinical trials, and follow-up data beyond 12–18 months are limited. The aim of this 24-month prospective observational study is to comprehensively describe the clinical outcomes of an Italian cohort of SMA I patients treated with OA. Methods: Based on recent literature, patients' treatment status was categorized as: monotherapy (OA only), bridge therapy (transition to OA within 3 months of starting nusinersen or risdiplam), or switch therapy (transition to OA after > 3 months of 1st treatment). Linear mixed-effects models examined predictors of improvement (CHOP-INTEND), adjusting for baseline motor function, SMN2 copy number, age, and prior treatment. Descriptive analyses were used to show changes in motor, respiratory, and nutritional milestones. Results: The cohort included 64 patients: 27 monotherapy, 9 bridge, and 28 switch. All patients showed significant improvement over 24 months (β = 20.40 points/year, p < 0.001). Patients who switched showed slower improvement (β = −3.76, p = 0.038) compared to monotherapy, while those who bridged showed no difference. Older age at treatment was associated with slower improvement (β = −1.48 points/year per month, p = 0.002). Of 49 non-sitters at baseline, 39 (80%) achieved sitting and 5 (10%) achieved walking. No new safety signals emerged in the second year of follow-up. Interpretation: Age and baseline motor functional status significantly influence outcomes; however, substantial confounding, particularly the initial treatment, limits the ability to isolate individual effects. Longer follow-up is essential for evaluating therapeutic responses in heterogeneous SMA I populations.
Onasemnogene Abeparvovec in Type I Spinal Muscular Atrophy: 24-Month Follow-Up From the Italian Registry / Pane, M.; Coratti, G.; Cutri, C.; Varone, A.; Masson, R.; D'Amico, A.; Sansone, V.; Messina, S.; Ricci, F.; Ticci, C.; Bruno, C.; Agosto, C.; Benedetti, F.; Pini, A.; Siliquini, S.; Filosto, M.; Zambon, A.; Bitetti, I.; Manna, M. R.; Dosi, C.; Zanin, R.; Parravicini, S.; De Sanctis, R.; Stanca, G.; Catteruccia, M.; Tosi, M.; Mizzoni, I.; Albamonte, E.; Franchino, V.; Sframeli, M.; Cavallina, I.; Procopio, E.; Sacchini, M.; Morando, S.; Brolatti, N.; Trucco, F.; Scarpini, G.; Briganti, E.; Berti, B.; Palermo, C.; Leone, D.; Previtali, S. C.; Mercuri, E.. - In: ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY. - ISSN 2328-9503. - (2026). [10.1002/acn3.70356]
Onasemnogene Abeparvovec in Type I Spinal Muscular Atrophy: 24-Month Follow-Up From the Italian Registry
Zambon A.;Previtali S. C.;
2026-01-01
Abstract
Objective: Onasemnogene abeparvovec (OA) is an AAV9-based gene therapy for spinal muscular atrophy type I (SMA I). Real-world outcomes show increased response variability compared to clinical trials, and follow-up data beyond 12–18 months are limited. The aim of this 24-month prospective observational study is to comprehensively describe the clinical outcomes of an Italian cohort of SMA I patients treated with OA. Methods: Based on recent literature, patients' treatment status was categorized as: monotherapy (OA only), bridge therapy (transition to OA within 3 months of starting nusinersen or risdiplam), or switch therapy (transition to OA after > 3 months of 1st treatment). Linear mixed-effects models examined predictors of improvement (CHOP-INTEND), adjusting for baseline motor function, SMN2 copy number, age, and prior treatment. Descriptive analyses were used to show changes in motor, respiratory, and nutritional milestones. Results: The cohort included 64 patients: 27 monotherapy, 9 bridge, and 28 switch. All patients showed significant improvement over 24 months (β = 20.40 points/year, p < 0.001). Patients who switched showed slower improvement (β = −3.76, p = 0.038) compared to monotherapy, while those who bridged showed no difference. Older age at treatment was associated with slower improvement (β = −1.48 points/year per month, p = 0.002). Of 49 non-sitters at baseline, 39 (80%) achieved sitting and 5 (10%) achieved walking. No new safety signals emerged in the second year of follow-up. Interpretation: Age and baseline motor functional status significantly influence outcomes; however, substantial confounding, particularly the initial treatment, limits the ability to isolate individual effects. Longer follow-up is essential for evaluating therapeutic responses in heterogeneous SMA I populations.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
