勒伯遗传性视神经病变基因疗法:视觉功能和解剖学测量之间的纵向关系
Byron L Lam1, William J Feuer1, Vittorio Porciatti1
1From the Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA.
American journal of ophthalmology
|September 16, 2023
概括
针对勒伯遗传性视神经病变 (LHON) 的基因治疗没有显著改善视觉功能. 解剖学测量表明视网膜逐渐变薄,这表明无症状眼睛的神经保护的潜在限制.
科学领域:
- 眼科医生 眼科 眼科
- 神经科学是一个神经科学.
- 遗传学 是一个遗传学.
背景情况:
- 勒伯遗传性视神经病变 (LHON) 是一种线粒体疾病,导致快速严重的视力丧失.
- G11778A突变是LHON的常见原因,影响ND4基因.
- 基因疗法旨在恢复线粒体功能,防止视神经退化.
研究的目的:
- 评估在G11778A LHON.基因治疗后视觉功能和解剖学变化之间的纵向关系.
- 评估内AAV2-P1ND4v2基因治疗在LHON不同阶段的安全性和潜在疗效.
主要方法:
- 一期临床试验,涉及因G11778A LHON.导致慢性,急性或单边视力丧失的患者.
- 单侧静脉内注射AAV2 ((Y444,500,730F) -P1ND4v2在不同的剂量.
- 结果措施包括视觉敏度,视野,电视网膜学,OCT成像 (RNFL和GCIPL厚度) 和视觉功能问卷.
主要成果:
- 稳定状态模式电网红图 (SS-PERG) 的振幅仍然较小,在治疗期间没有变化.
- 在所有眼睛中都观察到质细胞+内状层 (GCIPL) 和视网膜神经纤维层 (RNFL) 的显著和渐进的稀薄.
- 最好的视力敏度 (BCVA) 和视野平均偏差 (VF MD) 显示波动,没有明显的治疗效果.
- 在患有单边视力损失的患者中,视觉功能问卷分数下降.
结论:
- 在LHON患者中,基因疗法可能无法为无症状眼睛提供有效的神经保护,特别是当GCIPL和SS-PERG已经受损时.
- 随着LHON的自然史变化,治疗疗效的评估变得更加复杂.
- 未来的研究应该包括随机的,未经治疗的对照组,以更好地评估基因治疗结果.
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