中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (7): 2011-2012.doi: 10.4103/NRR.NRR-D-24-00504

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

脊髓性肌萎缩症的基因治疗：优化 SMN1 递送以纠正所有神经和系统紊乱的可能性观点

  

  • 出版日期:2025-07-15 发布日期:2024-11-26

Gene therapy for spinal muscular atrophy: perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

Sharon J. Brown, Rafael J. Yáñez-Muñoz, Heidi R. Fuller*   

  1. School of Pharmacy and Bioengineering, Keele University, Keele, UK (Brown SJ, Fuller HR)  Wolfson Center for Inherited Neuromuscular Disease, TORCH Building, RJAH Orthopaedic Hospital, Oswestry, UK (Brown SJ, Fuller HR)  AGCTlab.org, Center of Gene and Cell Therapy, Department of Biological Sciences, School of Life Sciences and the Environment, Royal Holloway University of London, Egham, UK (Yáñez-Muñoz RJ)
  • Online:2025-07-15 Published:2024-11-26
  • Contact: Heidi R. Fuller, PhD, h.r.fuller@keele.ac.uk.
  • Supported by:
    This work was supported by the Faculty Research Fund (Faculty of Medicine & Health Science, Keele University) Career Development Award–(April 2022) (to SJB).

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摘要： https://orcid.org/0000-0002-2858-869X (Heidi R. Fuller)

Abstract: Spinal muscular atrophy (SMA) is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and atrophy. The genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1 (SMN1) gene was identified as the main contributing factor (Lefebvre et al., 1995). This, in combination with the discovery that humans have a “backup” gene, SMN2, which can produce low levels (approximately 10%) of the full-length functional SMN protein, has led to the generation of SMAspecific gene therapies. SMA was traditionally classified according to age of symptom onset and developmental milestones achieved, with life expectancy and severity varying between individuals. Now, SMN2 copy number is used as a proxy for the prediction of disease severity, with higher SMN2 copy number typically being associated with reduced severity of SMA, although this relationship is not absolute: some individuals with low SMN2 copy number have less severe SMA phenotypes and vice versa. Additionally, the etiology of SMA is further complicated by other factors, such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.