InnerQuest NC Psychiatry and Counseling

Cancer Drug Shows Promise For Alzheimer Disease

Science online recently reported that an FDA approved cancer drug shows tremendous promise in treating Alzheimer Disease (AD). An association between the presence of beta-amyloid and the development of AD was discovered nearly two decades ago. It is unclear if the beta-amyloid deposition causes dementia or is simply associated with the condition. Researchers at Case Western Reserve University in Cleveland found that bexarotene, a cancer drug used to treat T-cell lymphoma, cleared beta-amyloid deposits from the brains of mice that are a model of AD. Background Apolipoprotein E (APoE) is a class of molecules that binds to a specific receptor on liver (& other) cells and is essential for transport and metabolism of triglyceride rich lipoprotein, fat-soluble vitamins, and cholesterol. In addition to its role in lipid metabolism that is involved in cardiovascular disease, APoE also seems to play important roles in AD and immune system regulation. In the nervous system, astroglial and microglial cells are the primary producers of APoE while neurons primarily make receptors for APoE. The "glial" cells can be thought of like scaffolding that provides structure and support for neurons the cells that are thought to be the messengers within our nervous system. APoE is a protein and there are three different but related genes that have been found in human beings that are responsible for making this protein. One of these genes, APoE-4, is implicated in AD and a few other conditions. Among Caucasians and Japanese carriers of this APoE-4 gene, there is between a 10 and 30 times increased risk of developing AD by age 75 when compared to those not carrying the gene. AD is characterized by deposits of a peptide beta-amyloid. APoE enhances the breakdown of this peptide. Clearly there are often other contributing factors to the development of AD since one third of those with AD do not have the APoE-4 gene and even some people who carry two APoE-4 genes (homozygous) do not develop AD. Another variant of the APoE gene, APoE-2 may offer some degree of protection against developing AD. Bexarotene is approved for the treatment of a T-cell lymphoma that comprise about 1 in 10 lymphomas. It boosts the production of APoE and this leads to more efficient clearance of beta-amyloid. The brains of AD sufferers contain plaques comprised of beta-amyloid. Theoretically, a substance that increases production of APoE may be expected to improve the clearance of beta-amyloid and thereby improve the functioning of AD sufferers. Facts About AD An estimated 5.4 million Americans of all ages have Alzheimer’s disease in 2012. This figure includes 5.2 million people age 65 and older(47), A1 and 200,000 individuals under age 65 who have younger-onset Alzheimer’s.(48) • One in eight people age 65 and older (13 percent) has Alzheimer’s disease.A2 • Nearly half of people age 85 and older (45 percent) have Alzheimer’s disease.A3 • Of those with Alzheimer’s disease, an estimated 4 percent are under age 65, 6 percent are 65 to 74, 44 percent are 75 to 84, and 46 percent are 85 or older. New Finding The study, conducted by Dr. Gary Landreth and published online in Science on February 9, 2012, found that in AD mice with significant accumulation of plaques administration of bexarotene removed 30% of plaques after 72 hours of treatment and 50% were removed after seven days. The microglial cells were activated and increased their rate of removal of beta-amyloid. Furthermore, the behavioral deficits that are seen in the AD mice with plaque accumulation was reversed within 72 hours of administration. These benefits persisted even after the bexarotene was stopped. Dr. Landreth hopes to secure FDA approval for Phase 1 human trials in healthy volunteers and the dosage will be much lower than the doses used in chemotherapy. Since the goal of eventual therapies developed from this discovery would be to maintain elevated levels of APoE and not necessarily to produce ever increasing amounts of APoE, a therapeutic dose might only be given several times each month. It remains to be seen if the startling results obtained in the mouse model will be reproduced in humans. One very interesting possibility that these findings point to is that the bexarotene appears to have cleared per-existing plaques. To date, most AD treatments have been directed at slowing or preventing the deposition of new plaques. For the estimated 5.4 million Americans with AD and millions more around the world, these findings are great news!   Links: Leonard Cruz, M.D. innerQuest Psychiatry & Counseling