Dados do Trabalho

Título

GENE THERAPY TREATMENT IN SMA WITH POSITIVE AAV9 ANTIBODIES

Apresentação do caso

Objective: To describe the outcome of the clinical evolution of two SMA patients with positive test for the AAV9 antibody, treated with gene therapy. Case report: Patient 1, C.M.M., currently 2 years and 11 months, was diagnosed with spinal muscular atrophy type C at 7 months due to the loss of cervical tonus and reduction of lower limbs movement, associated with weight loss caused by the dysphagia, with initiation of Spinraza treatment at 10 months. At 33 months, he received gene therapy, with a positive test for the AAV9 antibody (titer 1:100). The patient had no adverse events, only a slight increase in the transaminases, not higher than twice the reference value. Only two weeks after receiving the gene therapy, it was already possible to observe effective cough and improvement in torso strength; After 45 days, he was able to stand with only a short orthosis. Patient 2, T.E.S., currently 2 years and 3 months old, was diagnosed with SMA type 2 at 17 months of age. He started treatment with nusinersena at 19 months of age. At 25 months old, he received an infusion of gene therapy (Zolgensma) for SMA with an AAV9 test titer of 1:100, while two weeks earlier the titer was 1:200. He received 1mg/kg/day of prednisolone, without the need to increase the dose. He did not present any major adverse event, other than an increase in the transaminases up to 4 times the reference value, which allowed the suspension of the corticosteroid therapy 60 days after the infusion.

Discussão

Discussion: The cases in question are part of the presentation of SMA, which were early diagnosed due to the precocious identification of suggestive symptoms of the disease, such as generalized muscle hypotonia, areflexia and loss of developmental milestones. The possibility of early treatment, associated with non-pharmacological therapies, allows greater possibility of motor skill gains and improvement in quality of life. Although current drug leaflet guidelines only recommend the use of gene therapy for the treatment of SMA in patients with AAV9 antibody titers below 1:50, two patients with titers of 1:100 received the treatment and did not show any immunological side effect. On the contrary, after 2 weeks, they were already showing motor skill improvements.

Comentários finais

Final comments: Based on the cases presented, it is suggested the possibility of considering a higher titration for AAV9 antibodies to avoid the gene therapy in SMA patients.

Referências (se houver)

Fonte de Fomento (se houver)

Keywords: Spinal muscular atrophy. Neuromuscular disease. Muscular hypotonia. Gene therapy.

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Área

Doenças neuromusculares