title: Can Vitamin A be Improved to Prevent Blindness due to Age-Related Macular Degeneration, Stargardt Disease and Other Retinal Dystrophies?
abstract: 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.
authors.affiliation: Alkeus Pharmaceuticals, Inc., 21 Drydock Ave 6th Floor, 02210, Boston, MA, USA. leonide@alkeus.com.
authors.forename: Leonide
authors.initials: L
authors.lastname: Saad
authors.affiliation: Department of Ophthalmology, Columbia University Medical Center, Eye Research, 10032, New York, NY, USA. iw2101@columbia.edu.
authors.forename: Ilyas
authors.initials: I
authors.lastname: Washington
mesh_terms: D001766:Blindness / Q000209:etiology / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D003903:Deuterium / Q000737:chemistry; D019281:Dimerization; D006801:Humans; D008268:Macular Degeneration / Q000150:complications / Q000151:congenital* / Q000517:prevention & control*; D008956:Models, Chemical; D008968:Molecular Conformation / Q000187:drug effects; D015394:Molecular Structure; D010647:Phenyl Ethers / Q000627:therapeutic use; D011412:Propanolamines / Q000627:therapeutic use; D058499:Retinal Dystrophies / Q000150:complications / Q000517:prevention & control*; D000080362:Stargardt Disease; D014801:Vitamin A / Q000737:chemistry / Q000627:therapeutic use*; D014815:Vitamins / Q000737:chemistry / Q000627:therapeutic use
chemical_list: D010647:Phenyl Ethers; D011412:Propanolamines; D014815:Vitamins; C000592692:emixustat; D014801:Vitamin A; D003903:Deuterium
keywords: A2E; ABCA4; ALK-001; AMD; Age-related macular degeneration; Bisretinoids; C20-D3-vitamin A; Lipofuscin; Retinal dystrophies; Retinaldehyde; Stargardt; Visual cycle; Vitamin A; Vitamin A dimer