系统性基因疗法在诺里病模型中拯救了视网膜功能障碍和听力损失
Valda Pauzuolyte1,2, Aara Patel1,2, James R Wawrzynski1,2
1UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
EMBO molecular medicine
|August 29, 2023
概括
使用AAV9的基因治疗成功治疗了小鼠的诺里病. 新生儿治疗预防了听力损失和失明,为治疗这种遗传性疾病提供了希望.
科学领域:
- 眼科医生 眼科 眼科
- 遗传学 遗传学 是一个
- 耳鼻喉科 耳鼻喉科 耳鼻喉科
背景情况:
- 诺里病是一种遗传性疾病,由于NDP基因突变导致失明和渐进性听力损失.
- 它导致双重感官剥夺,目前治疗选择有限.
- 诺里病小鼠模型 (Ndptm1Wbrg) 呈现出类似的视网膜和耳病理.
研究的目的:
- 在诺里病小鼠模型中评估腺相关病毒载体 (AAV) 9介导的NDP基因治疗的治疗潜力.
- 研究AAV9-NDP在不同病理阶段 (新生儿,青少年,年轻成人) 的疗效.
- 评估治疗对视网膜血管化,耳毛细胞存活率和听觉功能的影响.
主要方法:
- 将携带人类NDPcDNA的AAV9静脉注射给诺里病小鼠.
- 在新生儿,青少年和年轻成年阶段进行治疗.
- 通过视网膜成像,电网膜图,耳组织学,RNA测序和听觉功能测试来评估治疗效果.
主要成果:
- 新生儿AAV9-NDP基因疗法预防了感官耳毛细胞死亡和正常化耳疾病生物标志物.
- 通过新生儿治疗,视网膜血管化和电网红图恢复到正常水平.
- 在疾病发作后进行的基因疗法也改善了耳病理,证明了对渐进性听力损失的治疗潜力.
结论:
- 以AAV9为媒介的NDP基因疗法是治疗诺里病的一种有前途的方法.
- 早期 (新生儿) 干预在预防感官损失方面非常有效.
- 该疗法显示出治疗诺里病患者渐进性听力损失的潜力,即使在疾病发作后.
相关概念视频
00:59Gene Therapy
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
00:59Gene Therapy
Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...