Alzheimer’s disease is an incredibly unfortunate and debilitating brain disease thought to be caused by abnormal protein build-up. One protein is called amyloid, which are deposits that form plaque around brain cells. The other thought to be involved is tau, which forms tangles within brain cells (NIH, nd). Neurotransmitters are also known to be decreased in the disease, such as acetylcholine. The exact mechanism is still not understood, and the disease can take years to show symptoms and progress. There are several factors that contribute to the disease, such as genetic factors, environmental factors, and lifestyle choices. Over time, those affected lose their ability to function on their own.
One of the most recent treatments being discussed is Aducanumab by Biogen Labs. Aducanumab is an investigational human monoclonal antibody that attempts to target the disease’s underlying pathophysiology to slow cognitive decline for patients. If it were to be approved, it would be the first treatment for individuals with Alzheimer’s. In their widely debated results, Biogen reported their participants who received the drug were able to retain their memory and perform daily tasks longer than patients who received the placebo (Chen, 2020). Aducanumab works to bind to the amyloid-beta proteins as an antibody. This is supposed to allow the immune system to target the amyloid-beta plaques and clear the plaques from the brain. Aducanumab did not stop the decline, but Biogen reports it slowed the decline of cognition in patients during memory and cognitive tasks. As of November 6th, 2020, the FDA Advisory Committee voted not to approve the novel drug. “In the final vote, which assessed whether or not the findings from the EMERGE trial (Study 302)—in the context of information from studies 301, 302, 103, and pharmacodynamic data—could serve as primary evidence for the effectiveness of Aducanumab in Alzheimer disease, the committee voted 10–0 (10 no; 0 yes; 1 uncertain) that the trial did not provide such evidence” (Neurology Live, 2020).
This was a disappointing result for one of the most anticipated committee decisions of this year. Biogen was applauded for the clinical design of the trial but ultimately needed to have more consistent data. Many still believe there is potential for the Aducanumab drug, but only time will tell. Dr. Krishna Bharani spoke about his article, “Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer’s disease.” Previous studies have confirmed BDNF disruption to be a contributing factor to the development of Alzheimer’s disease. Bharani’s results indicated that lower densities of tBDNF and TrkB receptors were shown to correlate with an increased amount of amyloid-beta and pTau. Further, lower levels of BDNF were found to affect hippocampal amyloid development, and Alzheimer’s disease pathology could be affected by altered BDNF and TrkB receptors. This suggests that a potential treatment or therapy could involve the BDNF pathway mechanism. As Biogen’s drug primarily targeted the amyloid, Dr. Bharani’s results suggest the importance of further targeting the Tau proteins and BDNF factors.
Sources Used
Aducanumab Approval Not Recommended by FDA Advisory Committee. Neurology live. https://www.neurologylive.com/view/aducanumab-approval-not-recommended-by-fda-advisory-committee.
Bharani, K. L., Ledreux, A., Gilmore, A., Carroll, S. L., & Granholm, A. C. (2020). Serum pro-BDNF levels correlate with phospho-tau staining in Alzheimer's disease. Neurobiology of aging, 87, 49–59.
Chen, A. (2020, August 8). The FDA Is Reviewing Biogen's 'Breakthrough' Alzheimer's Treatment. https://www.wbur.org/commonhealth/2020/08/08/biogen-alzheimers-treatment-fda-review.
U.S. Department of Health and Human Services. What Causes Alzheimer's Disease? National Institute on Aging. https://www.nia.nih.gov/health/what-causes-alzheimers-disease.
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