Alzheimer's Disease: LXR Program

Vitae Pharmaceuticals’ LXR modulators are potentially disease modifying compounds with a novel mechanism of action that is complementary to APP-processing inhibitors.

Administration of synthetic LXR modulators has been shown to reduce brain amyloid load.  LXR modulators increase the expression of apoE and ABCA1 in the brain, enhancing the clearance of amyloid-beta (Aß).  Improved Aß clearance slows the formation of Aß plaques that accumulate in the brains of patients with Alzheimer’s disease, and is a novel strategy for slowing or even halting disease progression.

• An estimated 30 million patients worldwide have some form of Alzheimer’s disease, representing a large economic and social burden. In the US, the total costs-of-care for Alzheimer’s was estimated to be $172 billion in 2010.
• Recent genetic data provided proof of principle that reducing ß site-cleavage of APP may protect against AD.
• Twelve months after starting full-scale research efforts, Vitae Pharmaceuticals has discovered multiple series of novel LXR modulators. Proof-of-principle has been demonstrated in non-human primates that LXR activation in the brain leads to a decrease in brain Aß levels upon stimulation of the LXR-ABCA1-apoE axis.

Vitae Pharmaceuticals’ LXR modulators may be a first-in-class disease modifying agent for the treatment of AD either as monotherapy or in combination with an APP-processing inhibitor.