Academic and scientists acknowledge that research about Alzheimer’s Disease in 2016 was disappointing and relatively unproductive. This was particularly true when Solanezumbab, a promising new drug, failed to perform significantly in clinical trials.
Solanezumab targeted beta-amyloid protein, as other drugs have done. Targeting beta-amyloid protein makes sense. With Alzheimer’s, the brain is invaded by bacteria because its blood barrier has grown porous with age. The brain fights the invading bacteria by surrounding them with protein and encapsulating them, producing protein deposits called beta-amyloids. The bacteria die but the protein enclosures remain. With time, tau proteins gather around the enclosures and cause nerve cells to die around the site. Inflammation and more nerve cell death ensue and Alzheimer’s Disease arises.
Solanezumab was thought to be able to bind beta-amyloid and even chase it from the brain. However, it was not found to be particularly effective, at least with the dosages and time frames studied. More trials will be started, but clinical trials often suffer from the underfunded and undermanned. Frequently, there are insufficient number of volunteers to participate in these studies.
Trial and error in ‘amyloid hypothesis’ in Alzheimer’s research
Other drugs aimed at beta-amyloid have yielded similar results as Solanezumab. Some show promise if higher dosages and more time are allotted. Crenezumab, which is also scheduled for further trials, appears to deliver antibodies against beta-amyloid effectively at higher dosages. Other antibody drugs are undergoing clinical trials, also. The pharmaceutical company Merck’s drug, Verubecestat, is a BACE1 inhibitor and an enzyme that is involved in the production of beta-amyloid. If the enzyme is inhibited, the theory goes, beta-amyloid production is slowed or stopped.
Blocking amyloid beta is a key goal in present Alzheimer’s research. Yet some scientists question this premise. The authors of a report in Nature on the drug Aducanumab say that the failure of antibody drugs in trials bring the “amyloid hypothesis” into doubt. Yet the researchers found that Aducanumab at the right dosage and over the proper time significantly reduced amyloid-beta in the brain. The researchers recommend Aducanumab as a “disease-modifying” treatment for Alzheimer’s Disease.
Alternative approaches to Alzheimer’s research
Some drug therapies focus on the tau protein (the “tangles”) that gather around the amyloid-beta protein encasements. One approach against tau is a vaccine, AADvac1, which activates the immune system to pinpoint tau protein and halts the progression of Alzheimer’s Disease. The results of clinical testing of this promising vaccine will not be complete until 2019. Researchers also have been tackling the challenge of reversing Alzheimer’s Disease by treating brain inflammation. Beta-amyloid proteins and tau tangles trigger an immune response in the brain that produces inflammation. Inflammation is part of the brain changes that accompany Alzheimer’s. A drug that alters inflammation, CSP-1103 (also known as CHF 5074), is undergoing studies.
More holistic, multi-therapy approaches have also shown promise, including scrutiny of intestinal bacteria as culprits affecting the brain in Alzheimer’s, and are avenues being explored.
Although 2016 did not produce a drug to prevent or cure Alzheimer’s Disease, the year in was not wasted. Thomas Edison said his 1,000 attempts at making a lightbulb were not failures, but a way to determine 1,000 ways that a lightbulb does not work. Scientists looking for ways to cure or limit Alzheimer’s are following in Edison’s footsteps. Someday they’ll discover what works.
Alzforum. 2016-A Year in Research. December 31, 2016. Available online at http://www.alzforum.org/news/research-news/2016-year-research. Retrieved January 11, 2016.
Alzheimer’s Association. Treatment Horizon. Available online at http://www.alz.org/research/science/alzheimers_treatment_horizon.asp. Retrieved January 11, 2016.
Buck Institute for Research on Aging. Memory Loss Associated with Alzheimer’s Reversed for the First Time. Available at http://www.buckinstitute.org/buck-news/Memory-loss-associated-with-Alzheimers-reversed. Accessed on June 26, 2016.
Kennedy, Matthew E., Stamford, Andrew W., Chen, Xia, Cox, Kathleen, Cumming, Jared N., Dockendorf, Marissa F., et al. (November 2, 2016). The BACE1 inhibitor Verubecestat (MK-8931) reduces CNS b-amyloid in animal models and in Alzheimer’s disease patients. Science Translational Medicine, 8(363): 363ra150. Available at http://stm.sciencemag.org/content/8/363/363ra150. Retrieved November 19, 2016.
Murnane, K. (Sept. 1, 2016). A Possible Treatment for Alzheimer’s disease is Demonstrated in Clinical Trial. Forbes. Available online at http://www.forbes.com/sites/kevinmurnane/2016/09/01/a-possible-treatment-for-alzheimers-disease-is-demonstrated-in-a-clinical-trial/#2a490df739e8. Retrieved January 11, 2016.
Sevigny, J., Chiao, P., Bussiere, T., Weinreb, P. H., Williams, L., et al. (September 2016). The antibody aducanumab reduces Ab plaques in Alzheimer’s disease. Nature, 537: 50 – 70.