Clinical trial of cone photoreceptor transplantation for the treatment of retinal degeneration

视锥细胞移植治疗视网膜变性的临床试验

• 批准号: MR/V038559/1
• 负责人: Robin Ali
• 金额: $ 543.51万
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FV038559%2F1
• 关键词: Clinical; trial; cone; photoreceptor; transplantation

The human eye makes use of two types of light-sensing cells, rods and cones. Of the two, the cones, which are active in daylight and which confer detailed (reading) vision, are by far the most important for day-to-day life. In conditions like cone dystrophy or Stargardt disease, the cone cells die over time, and as the human body is unable to replace these cells, this results in severe vision impairment. In this project we aim to create a source of transplantable cone cells and test whether the transplantation of these cells into the human eye can restore the vision that is lost in patients with advanced cone dystrophy. In a previous project, we have shown that we can grow up human cones in the laboratory using methods that make them suitable for subsequent transplantation into patients. When we transplanted these cells into mice that lack all light-sensing cells, we could prove that the human cells survived and made connections with the nerve cells of the mouse. As a result, light-sensation was restored in the mouse eye and the animal's behaviour changed in response to light, indication that some vision was restored. The aim of this project is to (1) scale-up the cone production method to be able to make enough cells for treating the human eye, (2) produce a large batch of cones that passes the quality regulations for human use, and (3) transplant these cone cells into the eyes of up to 12 patients with advanced cone dystrophy. As this is the first time that we test these cells the primary objective of the patient study will be to establish whether the transplantation of cones is safe. The secondary objective is to determine whether the transplanted cone cells can survive and restore vision, using a range of vision tests. If the study is successful, we will develop the transplantation method further to be able to treat a increasing range of blinding diseases.

人眼利用两种类型的感光细胞，杆和锥。在这两者中，视锥细胞在日光下活跃，并赋予详细的（阅读）视觉，是迄今为止对日常生活最重要的。在视锥细胞营养不良或Stargardt病等情况下，视锥细胞会随着时间的推移而死亡，由于人体无法替代这些细胞，这会导致严重的视力障碍。在这个项目中，我们的目标是创造一个可移植的视锥细胞来源，并测试这些细胞移植到人眼中是否可以恢复晚期视锥营养不良患者失去的视力。在之前的一个项目中，我们已经证明，我们可以在实验室中使用适合随后移植到患者体内的方法来培养人类视锥细胞。当我们将这些细胞移植到缺乏所有感光细胞的小鼠体内时，我们可以证明人类细胞存活下来，并与小鼠的神经细胞建立了联系。结果，小鼠眼睛恢复了光感，动物的行为对光的反应发生了变化，这表明一些视力得到了恢复。该项目的目的是（1）扩大视锥细胞的生产方法，使其能够生产足够的细胞用于治疗人眼，（2）生产大量符合人类使用质量规定的视锥细胞，（3）将这些视锥细胞移植到多达12名晚期视锥细胞营养不良患者的眼中。由于这是我们第一次测试这些细胞，因此患者研究的主要目的是确定视锥细胞移植是否安全。第二个目的是使用一系列视力测试来确定移植的视锥细胞是否可以存活并恢复视力。如果研究成功，我们将进一步开发移植方法，以治疗越来越多的致盲性疾病。