Developmental Neurosciences, Zayed Centre for Research into Rare Disease in Children, UCL Great Ormond Street Institute of Child Health, UCL, London, UK.
Department of Paediatric Neurology, Great Ormond Street Hospital for Children, London, UK.
Tremor Other Hyperkinet Mov (N Y). 2021 Nov 24;11:51. doi: 10.5334/tohm.661. eCollection 2021.
Neurodegeneration with brain iron accumulation (NBIA) disorders comprise a group of rare but devastating inherited neurological diseases with unifying features of progressive cognitive and motor decline, and increased iron deposition in the basal ganglia. Although at present there are no proven disease-modifying treatments, the severe nature of these monogenic disorders lends to consideration of personalized medicine strategies, including targeted gene therapy. In this review we summarize the progress and future direction towards precision therapies for NBIA disorders.
This review considered all relevant publications up to April 2021 using a systematic search strategy of PubMed and clinical trials databases.
We review what is currently known about the underlying pathophysiology of NBIA disorders, common NBIA disease pathways, and how this knowledge has influenced current management strategies and clinical trial design. The safety profile, efficacy and clinical outcome of clinical studies are reviewed. Furthermore, the potential for future therapeutic approaches is also discussed.
Therapeutic options in NBIAs remain very limited, with no proven disease-modifying treatments at present. However, a number of different approaches are currently under development with increasing focus on targeted precision therapies. Recent advances in the field give hope that novel strategies, such as gene therapy, gene editing and substrate replacement therapies are both scientifically and financially feasible for these conditions.
This article provides an up-to-date review of the current literature about Neurodegeneration with Brain Iron Accumulation (NBIA), with a focus on disease pathophysiology, current and previously trialed therapies, and future treatments in development, including consideration of potential genetic therapy approaches.
神经退行性脑铁沉积病（NBIA）是一组罕见但严重的遗传性神经退行性疾病，其特征为进行性认知和运动功能下降，基底节铁沉积增加。虽然目前尚无有效的疾病修饰治疗方法，但这些单基因疾病的严重性质促使人们考虑采用个体化药物治疗策略，包括靶向基因治疗。在本综述中，我们总结了 NBIA 疾病精准治疗的进展和未来方向。
本综述通过系统检索 PubMed 和临床试验数据库，纳入截至 2021 年 4 月的所有相关文献。
我们回顾了 NBIA 疾病的潜在病理生理学、常见 NBIA 疾病途径以及这些知识如何影响当前的管理策略和临床试验设计方面的已知内容。还回顾了临床研究的安全性、疗效和临床结果。此外，还讨论了未来治疗方法的潜力。
NBIA 中的治疗选择仍然非常有限，目前尚无有效的疾病修饰治疗方法。然而，目前有许多不同的方法正在开发中，越来越关注靶向精准治疗。该领域的最新进展表明，基因治疗、基因编辑和底物替代疗法等新策略在科学和经济上都适用于这些疾病。
本文提供了一份关于神经退行性脑铁沉积病（NBIA）的最新文献综述，重点关注疾病的病理生理学、当前和以前试验过的治疗方法以及正在开发的未来治疗方法，包括对潜在基因治疗方法的考虑。
