Fatal thrombotic microangiopathy case following adeno-associated viral SMN gene therapy

Adeno-associated virus (AAV) gene therapies are highly promising, such as the onasemnogene abeparvovec (Zolgensma) in spinal muscle atrophy (SMA). We report the first case of fatal systemic thrombotic microangiopathy (TMA) following onasemnogene abeparvovec in a 6-month-old child with SMA type 1, carrying a potential genetic predisposition in the complement factor I gene. Other cases of TMA have recently been reported after onasemnogene abeparvovec and after AAV9 minidystrophin therapy in Duchenne muscular dystrophy. The risk-benefit ratio of this therapy must therefore be assessed. Early recognition of TMA and targeted immunotherapy are fundamental to ensure the safety of patients treated with AAV gene therapies.

Automated summary

AAV gene therapies, such as onasemnogene abeparvovec, show great promise in treating spinal muscle atrophy (SMA). However, fatal systemic thrombotic microangiopathy (TMA) has been reported following the use of onasemnogene abeparvovec, raising concerns about the risk-benefit ratio of this therapy. Early recognition and targeted immunotherapy are crucial to ensure patient safety.