Off-the-shelf hypoimmunogenic photoreceptors for treatment of blinding retinal disease
现成的低免疫原性光感受器用于治疗致盲性视网膜疾病
基本信息
- 批准号:EP/Y031016/1
- 负责人:
- 金额:$ 269.72万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2024
- 资助国家:英国
- 起止时间:2024 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Blindness represents an increasing global problem with socio-economic impacts for the patients and society in general. Degenerative retinal diseases account for approximately 26% of global blindness affecting ~ 34 million people in the EU. Gene therapy, optogenetic tools, photosensitive switches and retinal prostheses have shown promising outcomes for restoring vision, but these are high-cost therapies applicable only to a small number of patients. The eye is suitable for transplantation so replacing dysfunctional photoreceptors should be feasible as long as sources of such cells are readily available. Pluripotent stem cells (PSCs) can generate cone and rod photoreceptors, which are able to integrate into the host retina and rescue vision in pre-clinical models of advanced retinal degeneration, but efficient long-term integration of allogeneic PSC-derived photoreceptors is impeded by the host immune response. To overcome this barrier and make this treatment accessible to a large number of patients with photoreceptor degeneration, I propose to: (1) generate off-the-shelf, immune-transparent (hypoimmunogenic) PSC-derived photoreceptors; (2) assess their effectiveness in evading the host immune system and (3) determine their long-term integration and ability to restore vision in pre-clinical models of advanced retinal degeneration. This novel high-gain approach provides a game-changing, effective and scalable photoreceptor transplantation platform, and a much-needed paradigm shift that will improve the quality of life for the millions of sufferers with blinding retinal disease. Through my involvement in successful phase I/II clinical trials of reversing corneal blindness via transplantation of limbal stem cells, I have had a unique opportunity to translate my research findings into treatments for patients with this rare disease. I now aim to build and validate a novel cell transplantation platform that will revolutionise the treatment of retinal degeneration.
失明是一个日益严重的全球性问题,给患者和整个社会带来了社会经济影响。退行性视网膜疾病约占全球失明的26%,影响着欧盟约3400万人。基因疗法、光遗传工具、光敏开关和视网膜假体在恢复视力方面显示出有希望的结果,但这些都是仅适用于少数患者的高成本疗法。眼睛适合移植,所以只要有现成的细胞来源,更换功能失调的光感受器应该是可行的。在晚期视网膜变性的临床前期模型中,多能干细胞(PSCs)可以产生视锥和视杆感受器,这些感受器能够整合到宿主视网膜并挽救视力,但同种异体PSC来源的感光细胞的有效长期整合受到宿主免疫反应的阻碍。为了克服这一障碍并使大量的光感受器变性患者能够获得这种治疗方法,我建议:(1)产生现成的、免疫透明(低免疫原性)的PSC来源的光感受器;(2)评估它们在逃避宿主免疫系统方面的有效性;(3)在晚期视网膜变性的临床前模型中确定它们的长期整合和恢复视力的能力。这一新的高增益方法提供了一个改变游戏规则、有效和可扩展的光感受器移植平台,以及一个亟需的范式转变,将改善数百万失明视网膜疾病患者的生活质量。通过参与成功的通过角膜缘干细胞移植逆转角膜失明的I/II期临床试验,我有一个独特的机会将我的研究成果转化为对这种罕见疾病患者的治疗。我现在的目标是建立和验证一个新的细胞移植平台,它将彻底改变视网膜变性的治疗方法。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Majlinda Lako其他文献
Animal Models for Limbal Stem Cell Deficiency: A Critical Narrative Literature Review
- DOI:
10.1007/s40123-023-00880-0 - 发表时间:
2024-01-27 - 期刊:
- 影响因子:3.200
- 作者:
Eray Atalay;Burcugül Altuğ;Mert Egemen Çalışkan;Semih Ceylan;Zeynep Serra Özler;Gustavo Figueiredo;Majlinda Lako;Francisco Figueiredo - 通讯作者:
Francisco Figueiredo
Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity
多能干细胞衍生的视网膜疾病模型:阐明发病机制、评估新疗法和评估毒性
- DOI:
10.1016/j.preteyeres.2024.101248 - 发表时间:
2024-05-01 - 期刊:
- 影响因子:14.700
- 作者:
Marzena Kurzawa-Akanbi;Nikolaos Tzoumas;Julio C. Corral-Serrano;Rosellina Guarascio;David H. Steel;Michael E. Cheetham;Lyle Armstrong;Majlinda Lako - 通讯作者:
Majlinda Lako
Unravelling genotype-phenotype correlations in Stargardt disease using patient-derived retinal organoids
利用患者来源的视网膜类器官解开斯特格病中的基因型-表型相关性
- DOI:
10.1038/s41419-025-07420-7 - 发表时间:
2025-02-19 - 期刊:
- 影响因子:9.600
- 作者:
Avril Watson;Rachel Queen;Luis Ferrández-Peral;Birthe Dorgau;Joseph Collin;Andrew Nelson;Rafiqul Hussain;Jonathan Coxhead;Michael McCorkindale;Robert Atkinson;Darin Zerti;Valeria Chichagova;Ana Conesa;Lyle Armstrong;Frans P. M. Cremers;Majlinda Lako - 通讯作者:
Majlinda Lako
Majlinda Lako的其他文献
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{{ truncateString('Majlinda Lako', 18)}}的其他基金
To assess the engraftment of hESC-derived photoreceptors and their ability to restore vision in early and advanced stages of Retinitis Pigmentosa.
评估 hESC 来源的光感受器的植入及其在色素性视网膜炎早期和晚期恢复视力的能力。
- 批准号:
MR/X001687/1 - 财政年份:2023
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
Elucidating splicing factor function and retinal splicing programmes: developing new therapeutic strategies for splicing factor retinitis pigmentosa
阐明剪接因子功能和视网膜剪接方案:开发剪接因子色素性视网膜炎的新治疗策略
- 批准号:
MR/T017503/1 - 财政年份:2020
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
Assessing SARS-CoV-2 entry, replication and prevention in a primary human conjunctival cell model and organ cultured cornea/conjunctiva.
评估原代人类结膜细胞模型和器官培养角膜/结膜中 SARS-CoV-2 的进入、复制和预防。
- 批准号:
BB/V01126X/1 - 财政年份:2020
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
A single cell sequencing approach to determine the heterogeneity, dynamics and cell fate decisions of retinal progenitor cells in vivo and in vitro
一种单细胞测序方法,用于确定体内和体外视网膜祖细胞的异质性、动态和细胞命运决定
- 批准号:
BB/T004460/1 - 财政年份:2020
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
Understanding the molecular and cellular complexity of human cornea through single cell analyses
通过单细胞分析了解人类角膜的分子和细胞复杂性
- 批准号:
MR/S035826/1 - 财政年份:2018
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
Using zinc finger nuclease technology to generate reporter-labelled human pluripotent stem cells as a tool to optimize photoreceptor transplantation
使用锌指核酸酶技术生成报告基因标记的人类多能干细胞作为优化光感受器移植的工具
- 批准号:
BB/I02333X/1 - 财政年份:2011
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
A state of the art multiparametric flow cytometry analysis system for multidisciplinary stem cell research
用于多学科干细胞研究的最先进的多参数流式细胞术分析系统
- 批准号:
BB/E012841/1 - 财政年份:2007
- 资助金额:
$ 269.72万 - 项目类别:
Research Grant
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