Combinatorial RXR-based therapeutics for Alzheimer's disease

DESCRIPTION (provided by applicant): The principle objective of this application is the development of safer and more effective combinatorial therapy for AD. ReXceptor, Inc. is developing new therapeutics for the treatment of AD based on stimulating the physiological clearance mechanisms of soluble forms of A from the brain. Bexarotene is an agonist of the ligand-activated transcription factor, retinoid X receptor (RXR), and stimulates the transcription of ApoE and its lipid transporters, leading to elevated levels of high density lipoproteins (HDL) i the brain. ApoE-based HDLs act to promote the proteolysis of A peptides, resulting in restoration of normal neural network function and improved memory and cognition. Bexarotene is an FDA approved drug for the treatment of cutaneous T-cell lymphoma with a favorable safety profile. However, oral administration of bexarotene is associated with hypertriglyceridemia and hypercholesterolemia. Thus, minimizing the side effects associated with cardiovascular risk is