• Kirk Hartley

Investing in Science and Faster, Better Clinical Trials – Possible Major Alzheimer’s B

The world cannot afford major diseases, and should be investing heavily in science. Yet, in the US, we see "budget hawks" blindly arguing for across the board budget cuts that would further reduce research budgets already too low. How can anyone in good conscience suggest that nations cut budgets focused on research of major diseases? And, when will politicians stop posturing over political footballs and focus instead on real needs, such as encouraging science and facilitating faster, better clinical trials for promising new treatments (statement of ASCO)

The points are highlighted by the possibility that there is now a major breakthrough in Alzheimer’s research. The news is out in a ScienceDaily summary of a new study published on Thursday in Science, a world class journal.

The news is big, as indicated by the article being published online on February 9, after being received on December 9, 2011. That’s fast for a journal. The story also is on Huffington Post, in Scientific American (excellent summary), the BBC, and the Wall Street Journal. The news also is key because the active agent – Bexarotene- already is approved for use in coping with a form of cancer, might be "only" $1,200 per month and is under study in various trials for cancer issues.

Translating this research into the clinic is of course not a sure thing and will take time. But, if it works at all well, consider the potential benefits in human misery avoided, and economic savings. Scientific research is key for our collective futures and deserves vastly more financial support than it receives today. Set out below are key excerpts from the ScienceDaily summary:

"ScienceDaily (Feb. 9, 2012) — Neuroscientists at Case Western Reserve University School of Medicine have made a dramatic breakthrough in their efforts to find a cure for Alzheimer’s disease. The researchers’ findings, published in the journalScience, show that use of a drug in mice appears to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer’s. The results point to the significant potential that the medication, bexarotene, has to help the roughly 5.4 million Americans suffering from the progressive brain disease.

Bexarotene has been approved for the treatment of cancer by the U.S. Food and Drug Administration for more than a decade. These experiments explored whether the medication might also be used to help patients with Alzheimer’s disease, and the results were more than promising.

Alzheimer’s disease arises in large part from the body’s inability to clear naturally-occurring amyloid beta from the brain. In 2008 Case Western Reserve researcher Gary Landreth, PhD, professor of neurosciences, discovered that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitated the clearance of the amyloid beta proteins. Landreth, a professor of neurosciences in the university’s medical school, is the senior author of this study as well.

Landreth and his colleagues chose to explore the effectiveness of bexarotene for increasing ApoE expression. The elevation of brain ApoE levels, in turn, speeds the clearance of amyloid beta from the brain. Bexarotene acts by stimulating retinoid X receptors (RXR), which control how much ApoE is produced.

In particular, the researchers were struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer’s disease. The present view of the scientific community is that small soluble forms of amyloid beta cause the memory impairments seen in animal models and humans with the disease. Within six hours of administering bexarotene, however, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer’s.

One example of the improved behaviors involved the typical nesting instinct of the mice. When Alzheimer’s-diseased mice encountered material suited for nesting — in this case, tissue paper — they did nothing to create a space to nest. This reaction demonstrated that they had lost the ability to associate the tissue paper with the opportunity to nest. Just 72 hours after the bexarotene treatment, however, the mice began to use the paper to make nests. Administration of the drug also improved the ability of the mice to sense and respond to odors.

Bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain. The plaques are compacted aggregates of amyloid that form in the brain and are the pathological hallmark of Alzheimer’s disease. Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reduction totaled 75 percent. It appears that the bexarotene reprogrammed the brain’s immune cells to "eat" or phagocytose the amyloid deposits. This observation demonstrated that the drug addresses the amount of both soluble and deposited forms of amyloid beta within the brain and reverses the pathological features of the disease in mice."


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