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Registry and Gene Replacement Therapy for Spinal Muscular Atrophy at Referral Center of Pediatrics in Vietnam

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical- Pediatric
  • Secondary Categories:
    • Clinical- Pediatric
Introduction:
Introduction: Spinal Muscular Atrophy (SMA) is an autosomal recessive disorder characterized by the loss of motor neurons, leading to progressive muscle weakness and atrophy. The incidence is approximately 1:10,000 live births and carriers is 1:50 in the population. Recent advancements have led to the regulatory approval of gene therapies like onasemnogene abeparvovec (OA), which has shown significant efficacy in clinical trials. These therapies represent a breakthrough in SMA treatment, potentially offering long-term improvements in motor function and quality of life for affected individuals. The first children with SMA were confirmed in Vietnam in 2002. The accumulated number of children with SMA is 899 cases (1.2002-10.2024) and 32 children with SMA received intravenous gene replacement therapy (2021-2023) at the Vietnam National Children’s Hospital in Hanoi (VNCH).

The aim of the study is to describe the phenotype and genotype and to evaluate the outcome of gene replacement therapy in SMA cases at VNCH.



 

Methods:
Methods: this is a case series study, 124 SMA cases included 67 boys and 57 girls (2021-2023). Clinical evaluation covered motor function and complication at the time of diagnosis. Thirty-two children received a single dose of intravenous OA [1.1 × 1014 vector genomes/kg body weight (vg/kg)] and were assessed for side effects, motor function, and complication after treatment.

 

Results:
Results: In the distribution of severity among 124 SMA cases, the proportions of SMA I, II, and III were 26.3%, 52.5%, and 22.2%, respectively. 78% of SMA I cases had respiratory insufficiency at the time of diagnosis; 81.5% of SMA II cases were able to sit independently at diagnosis, and most SMA III cases retained the ability to walk or walk with assistance at diagnosis. Scoliosis was more common in SMA II (23%) compared to SMA III (11%). Genotype included 123 cases with homozygous deletion of exon 7 of the SMN1 gene; one case was a compound heterozygous with one copy of exon 7 of SMN1 and a complex pathogenic variant (c.156-165delinsCA; p.Ala53LysfsX3) on the remaining allele.

Among the 32 SMA cases receiving intravenous OA therapy, there are 10 cases of SMA I and 22 cases of SMA II. The mean age at the time of treatment for SMA I and SMA II was 8 months (ranging from 1 to 25 months) and 18 months (ranging from 11 to 21 months), respectively. Two out of the 10 SMA I cases died from pneumonia one month and one year after receiving OA therapy, respectively. The remain 8 cases showed improvement in motor function according to the HINE scale: all 8 were able to sit without support, and 80% were living without ventilator support after 24-55 months. All SMA II cases showed improvement in motor function according to the HINE scale, with 3 cases able to walk. The site effects of intravenous OA included elevated ALT and AST levels (29/32), fever (15/32), neutropenia (14/32), thrombocytopenia (12/32), vomiting (5/32), and rash (2/32).

 

Conclusion:
Conclusions: SMA I was diagnosed late, with most cases already experiencing respiratory insufficiency. Intravenous OA gene replacement therapy was effective in improving motor function in almost all cases and increased the rate of ventilator-free survival in SMA I cases. Liver toxicity side effects were common.

 

Agenda

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