Blouin Laure, Sahel José-Alain, Chung Daniel C
Director of Clinical Science & Medical Communications, SparingVision, 75008 Paris, France.
Department of Ophthalmology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15219, USA.
Cold Spring Harb Perspect Med. 2024 Dec 2;14(12):a041665. doi: 10.1101/cshperspect.a041665.
Inherited retinal diseases (IRDs) are the leading cause of blindness in working-age individuals worldwide. Their genetic etiology is especially heterogenous, so the development of gene-specific therapies is unlikely to meet the medical needs of the entire patient community. Considering these challenges, a complementary strategy could be to develop therapies independent of the underlying gene variant causing retinal degeneration. As the retina is a neural tissue, it is in theory amenable to neuroprotective therapies that could help prolong cell survival or promote retinal function. Many neurotrophic factors have shown favorable results in preclinical animal models of neurodegenerative diseases, but unfortunately these findings have not yet translated into successful human clinical trials. The clinical development of these new therapies is mostly impeded by selection of pertinent clinical end points and time-to-readout, as the majority of IRDs show a relatively slow disease progression rate. Despite these challenges, several strategies have moved forward into clinical development.
遗传性视网膜疾病（IRDs）是全球劳动年龄人群失明的主要原因。其遗传病因特别具有异质性，因此基因特异性疗法的开发不太可能满足整个患者群体的医疗需求。考虑到这些挑战，一种补充策略可能是开发独立于导致视网膜变性的潜在基因变异的疗法。由于视网膜是一种神经组织，理论上它适合采用神经保护疗法，这种疗法有助于延长细胞存活时间或促进视网膜功能。许多神经营养因子在神经退行性疾病的临床前动物模型中显示出良好的效果，但不幸的是，这些发现尚未转化为成功的人体临床试验。这些新疗法的临床开发大多受到相关临床终点的选择和读出时间的阻碍，因为大多数IRDs显示出相对较慢的疾病进展速度。尽管存在这些挑战，仍有几种策略已进入临床开发阶段。
