MacDonald Ian M, Moen Christopher, Duncan Jacque L, Tsang Stephen H, Cehajic-Kapetanovic Jasmina, Aleman Tomas S
Department of Ophthalmology and Visual Sciences, University of Alberta, Edmonton, Canada.
Choroideremia Research Foundation, Springfield, MA, USA.
Transl Vis Sci Technol. 2020 Feb 14;9(3):17. doi: 10.1167/tvst.9.3.17.
To report combined viewpoints on ocular gene therapy from a select group of clinician scientists and a patient advocacy group.
With the support of Randy Wheelock and Dr. Chris Moen from the Choroideremia Research Foundation (CRF), a special interest group at the 2019 Annual meeting of the Association for Research in Vision and Ophthalmology in Vancouver, Canada, shared their knowledge, experience, concepts, and ideas and provided a forum to discuss therapeutic strategies for the treatment of inherited retinal disorders, using experience in choroideremia (CHM) as a model.
A member of the CRF presented the patient perspective and role in clinical trials. Five clinician scientists presented reasons for limited long-term visual improvement in many gene therapy trials, including challenges with dose, incomplete understanding of photoreceptor metabolism, vector delivery, inflammation, and identification of patients likely to benefit from treatment.
The shared experience of the five clinician scientists indicates that the results of ocular gene therapy for choroideremia have been less successful than for -related Leber congenital amaurosis. Improvement in vector delivery and developing a better understanding of gene expression in target tissues, treatment dose and side effects, and inflammation, as well as identifying patients who are most likely to benefit without suffering excessive risk, are necessary to advance the development of effective therapies for inherited retinal degenerations.
Additional long-term data are required to determine if ocular gene therapy will be sufficient to alter natural progression in choroideremia. Combination therapies may have to be considered, as well as alternative vectors that minimize risk.
报告一组临床医生科学家和一个患者权益倡导组织对眼部基因治疗的综合观点。
在脉络膜视网膜病变研究基金会（CRF）的兰迪·惠洛克（Randy Wheelock）和克里斯·莫恩（Chris Moen）博士的支持下，一个特别兴趣小组在加拿大温哥华举行的2019年视觉与眼科学研究协会年会上分享了他们的知识、经验、概念和想法，并提供了一个论坛，以脉络膜视网膜病变（CHM）为例，讨论遗传性视网膜疾病的治疗策略。
CRF的一名成员介绍了患者的观点以及在临床试验中的作用。五位临床医生科学家阐述了许多基因治疗试验中长期视觉改善有限的原因，包括剂量方面的挑战、对光感受器代谢的不完全理解、载体递送、炎症以及确定可能从治疗中受益的患者。
五位临床医生科学家的共同经验表明，脉络膜视网膜病变的眼部基因治疗结果不如相关的莱伯先天性黑蒙成功。改善载体递送、更好地理解靶组织中的基因表达、治疗剂量和副作用以及炎症，同时确定最有可能受益且风险不过高的患者，对于推进遗传性视网膜变性有效疗法的开发是必要的。
需要更多长期数据来确定眼部基因治疗是否足以改变脉络膜视网膜病变的自然病程。可能需要考虑联合疗法以及将风险降至最低的替代载体。
