Transthyretin (TTR) amyloidosis is a systemic, progressive, and fatal disease. TTR is integral in vitamin A (retinol) transport via its binding to retinol binding protein 4 (RBP4). Current and emerging therapies for TTR amyloid cardiomyopathy (ATTR-CM), including RNAi therapies and potentially CRISPR-based therapies, reduce hepatic transthyretin production and hence decrease serum RBP4, which decreases circulating vitamin A levels. However, despite these reductions in circulating vitamin A, hepatic reserves and alternative delivery mechanisms may prevent clinical manifestations of vitamin A deficiency. Vitamin A functions as a key regulator of immunity, antioxidant function, cell growth and differentiation and vision. This paper aims to serve as a comprehensive review of vitamin A and its metabolites, their transport, and their function in human health and disease. Additionally, we seek to synthesize the relevant outcomes and safety data of TTR silencing therapies and how they relate to circulating vitamin A levels and vitamin A-related clinical outcomes in a manner that is relevant to the cardiac amyloidosis specialist.
Brown et al. (Tue,) studied this question.