Based on co-drugs representing two different chemical entities and the co- and sequential administration of the two chemical entities, novel therapies for
macular degeneration and TTR
amyloidosis are provided. The first component (“Bispecific RBP4 / TTR ligand”) is a chemical entity that binds to both TTR and RBP4 in the RBP4 (
retinol-
binding protein 4)-TTR (
transthyretin) complex, which participates in the delivery of
retinol to the
retina. This component reduces
retinol transport from circulation to the
retina and provides stabilization of the TTR
tetramer. The second component (“C20-D3-visual
chromophore-generating compound”) is a C20-D3 modified
retinoid or
carotenoid that, when metabolized in mammals, ultimately produces a C20-D3 visual
chromophore, which is presented in the
retina as C20-D3-9-cis-
retinal or C20-D3-11-cis-
retinal. Deuteration at C20 reduces the formation of
lipofuscin biretinol, but other functions (such as providing a precursor for the synthesis of the visual
chromophore 11-cis-retinaldehyde
in vivo) are not reduced.