Onasemnogene abeparvovec en atrofia muscular espinal 5q: evidencia clínica, bases inmunobiológicas y retos para la práctica pediátrica

Esteban Zavaleta Monestel
Departamento de Investigación, Hospital Clínica Bíblica, San José, Costa Rica.

Resumen

La atrofia muscular espinal (AME) es una enfermedad neuromuscular autosómica recesiva causada por mutaciones bialélicas en SMN1, que conducen a deficiencia de proteína SMN y degeneración progresiva de neuronas motoras alfa. La introducción de terapias modificadoras, y en particular de la terapia génica onasemnogene abeparvovec, ha transformado la historia natural de la AME tipo 1 y ha consolidado el concepto de una ventana terapéutica crítica, especialmente en el contexto del cribado neonatal. Esta revisión integra evidencia clínica pivotal (START, STR1VE, SPR1NT), consideraciones prácticas para el pediatra (diagnóstico, selección, evaluación inmunológica, monitorización), bases mecanísticas de inmunogenicidad innata y adaptativa asociada al vector AAV9, y eventos adversos relevantes, incluyendo hepatotoxicidad grave, microangiopatía trombótica y alteraciones de troponina. Asimismo, se contextualiza el reemplazo génico frente a nusinersen y risdiplam, se discuten incertidumbres longitudinales vinculadas a persistencia episomal y ausencia de redosificación, y se incorporan consideraciones éticas y de equidad sanitaria derivadas del alto costo. Finalmente, se presenta una sección formal de limitaciones de la evidencia con implicaciones para investigación y práctica clínica.

Palabras claves

Atrofia muscular espinal; terapia génica; onasemnogene abeparvovec; AAV9; cribado neonatal; pediatría; seguridad; hepatotoxicidad.

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