Alzheimer's Diseases and Related Dementias
Neurodegenerative disorders, such as Alzheimer's disease (AD), afflict over 4 million men and women in the United States. Due, in part, to the increase in numbers of older men and women, the incidence of AD is rising. In fact, short of an effective method to treat AD, the Alzheimer's Association has predicted that by 2050, over 14 million men and women will suffer from the ravaging effects of AD. Today, there exists no particularly effective treatment — a result of scientists not fully understanding what abnormal processes in brain cause AD.

One of the characteristic events in AD is the accumulation of amyloid plaques between neurons in brain. Amyloid is comprised of protein fragments and its production and break down by cells is normal. However, in AD, fragments of amyloid called ß-amyloid accumulate to form plaques. Over time, these plaques cause neurons to malfunction and die. Published data suggest that elevated serum cholesterol may be a risk factor for the formation of ß-amyloid plaques. In addition, brain-specific factors that effect localized cholesterol metabolism may also be tied to ß-amyloid formation. Therefore, Anagen is conducting preliminary studies with its proprietary LXR ligands to evaluate the effect of these compounds on ß-amyloid accumulation.

Other Areas of Interest
Recent data also suggest that cholesterol in the brain may play a critical role in the generation of synapses among neurons. For example, large amounts of cholesterol turn over among glial cells and neurons during neuron repair and remodeling. If cholesterol indeed plays a fundamental role in the neuronal repair process, then the effects of biochemically — or physically — induced damage to neurons (e.g., stroke, trauma, disease, aging) may be attenuated by compounds that improve availability of cholesterol in brain. Interestingly, LXR-ß receptors are known to be present in brain and may play a role in cholesterol metabolism in this tissue. If so, the ability of a selective LXR modulator to promote cholesterol synthesis and release from glial cells could have far-reaching benefit in a variety of neurodegenerative diseases. Anagen intends to evaluate this hypothesis using its proprietary LXR ligands.