Saad Leonide, Washington Ilyas
Alkeus Pharmaceuticals, Inc., 21 Drydock Ave 6th Floor, 02210, Boston, MA, USA.
Department of Ophthalmology, Columbia University Medical Center, Eye Research, 10032, New York, NY, USA.
Adv Exp Med Biol. 2016;854:355-61. doi: 10.1007/978-3-319-17121-0_47.
We discuss how an imperfect visual cycle results in the formation of vitamin A dimers, thought to be involved in the pathogenesis of various retinal diseases, and summarize how slowing vitamin A dimerization has been a therapeutic target of interest to prevent blindness. To elucidate the molecular mechanism of vitamin A dimerization, an alternative form of vitamin A, one that forms dimers more slowly yet maneuvers effortlessly through the visual cycle, was developed. Such a vitamin A, reinforced with deuterium (C20-D3-vitamin A), can be used as a non-disruptive tool to understand the contribution of vitamin A dimers to vision loss. Eventually, C20-D3-vitamin A could become a disease-modifying therapy to slow or stop vision loss associated with dry age-related macular degeneration (AMD), Stargardt disease and retinal diseases marked by such vitamin A dimers. Human clinical trials of C20-D3-vitamin A (ALK-001) are underway.
我们讨论了不完美的视觉循环如何导致维生素A二聚体的形成，而维生素A二聚体被认为与各种视网膜疾病的发病机制有关，并总结了减缓维生素A二聚化如何成为预防失明的一个备受关注的治疗靶点。为了阐明维生素A二聚化的分子机制，人们开发了一种维生素A的替代形式，它形成二聚体的速度较慢，但能轻松地在视觉循环中运作。这种用氘强化的维生素A（C20-D3-维生素A），可作为一种无干扰工具来了解维生素A二聚体对视力丧失的影响。最终，C20-D3-维生素A可能成为一种改善病情的疗法，以减缓或阻止与干性年龄相关性黄斑变性（AMD）、斯塔加特病以及以这种维生素A二聚体为特征的视网膜疾病相关的视力丧失。C20-D3-维生素A（ALK-001）的人体临床试验正在进行中。
