Public implementation of expanded newborn screening for spinal muscular atrophy in Tochigi prefecture and a patient treated with onasemnogene abeparvovec after the negative conversion of anti-AAV9 antibody

Abstract

  Objective: With the availability of approved treatments for spinal muscular atrophy (SMA), early diagnosis and treatment are considered important and newborn screening (NBS) has commenced in some regions. From April 2022 to March 2023, expanded NBS for SMA and immunodeficiency was studied in Tochigi Prefecture. Methods: A real-time PCR method was performed using reagents capable of simultaneously detecting the SMN1 gene, causes SMA, and TREC and KREC, markers for immunodeficiency. Results: 10,738 of all newborns were screened. Detailed clinical examinations were undertaken in suspected cases of SMA (n＝1) and immunodeficiency (n＝4) and confirmed one case each of SMA and secondary immunodeficiency ; the remaining three cases were normal. At 16 days of age, the female patient with SMA had 0 and 3 copies of SMN1 and SMN2, respectively, and anti-AAV9 antibody titers ＞1 : 200. Before gene therapy, the patient’s muscle tone and strength and deep tendon reflexes were normal ; the CHOP INTEND was 30 points, and the CMAP of the median nerve was 1.2 mV, which were lower than the reference value. As the patient tested positive for anti-AAV9 antibody, from 23 days after birth, she was treated with nusinersen five times. At 8 months of age, the patient tested negative for anti-AAV9 antibody and initiated treatment with onasemnogene abeparvovec. At 1 year and 4 months of age, the patient was able to walk independently. Conclusions: In this case, early treatment resulted in almost typical development. NBS was shown to be useful. Therefore, accumulation of early diagnosis and treatment cases will facilitate the commercial availability of extended NBS to enable early treatment and effective management.