BACKGROUND:  Vitamin A participates in a variety of physiological functions, such as vision, neuronal signaling, spermatogenesis, and the maintenance of immune competence and epithelium integrity. Even though strong evidence for decades suggested the existence of a cell surface receptor for retinol binding protein (RBP), the receptor has remained elusive. Vitamin A homeostasis is altered in a variety of diseases, including visual and neurological disorders, cancers, diabetes, skin diseases, and immune disorders. Identifying the major physiological mechanism for cellular vitamin A uptake is an important step to develop specific and effective treatments for a wide range of human diseases associated with imbalance in retinoid levels.

INNOVATION:  Investigators at UCLA have identified the long-sought cell-surface receptor for RBP that mediates efficient and specific transport of vitamin A into cells. Consistent with the diverse physiological functions of vitamin A, the RBP receptor is expressed in diverse organs such as the eye, brain, spleen and skin. These organs are known to depend on vitamin A for proper function, and the RBP receptor is a promising drug target to modulate vitamin A uptake into cells or tissues. Activators and blockers of this receptor can be identified through a variety of screening methods, leading the way to candidate compounds that treat a variety of disorders.

POTENTIAL APPLICATIONS 

• Therapeutics to treat visual disorders, such as macular degeneration.
• Treatments for neurological disorders associated with imbalance in retinoid levels, including Parkinson's disease, depression, Huntington's disease, Alzheimer disease, and neuronal degeneration.
• Target the RBP receptor to inhibit the growth of cancer cells that depend on retinoids for cell proliferation.
• Reversal of skin aging by increasing vitamin A uptake of the skin through the RBP receptor.

ADVANTAGES

• Drugs that specifically target the RBP receptor allow for specific modulation of cellular vitamin A/retinoid levels.
• Drugs that specifically target the RBP receptor can avoid toxic effects of retinoid therapy, such as bone toxicity, serum lipid increments, disruption of hippocampal-dependent memory, and other undesirable consequences.
• Membrane receptors and transporters have been one of the most successful drug targets in the pharmaceutical industry.

DEVELOPMENT-TO-DATE:  The major physiological mechanism to increase cellular vitamin A/retinoid level has been identified. Investigators have developed various assays to study the effect of drugs on its biological activity.

Related Papers (Selected) Kawaguchi R, Yu J, Honda J, Whitelegge J, Ping P, Wiita P, Bok D, Sun H. A Membrane Receptor for Retinol Binding Protein Mediates Cellular Uptake of Vitamin A. Science, 2007 Feb 9;315(5813):820-5. (Link)

Reference: UCLA Case No. 2007-383