By: Grace Cheung
Alzheimer’s disease is a progressive, neurodegenerative disorder that slowly destroys brain cells and causes the deterioration of cognitive functions, such as memory, thinking, and language (1). It is estimated to affect over 5.5 million Americans, most of them aged 65 or older (2). Alzheimer’s is characterized by large clusters of amyloid-β (Aβ) plaques surrounded by neurons that contain neurofibrillary tangles. These excessive protein deposits are believed to cause the vascular damage and neuronal cell loss associated with neurodegeneration and disease progression (3).
In a recent study conducted by Biogen researchers discovered an antibody, known as aducanumab, that binds to aggregated amyloid-beta, potentially reducing the number of amyloid plaques present in the brain (1). Researchers completed three phase 1 trials measuring the effects of aducanumab in humans. A fourth, double-blind, placebo-controlled trial was designed to assess the effects of varying aducanumab doses on the levels of amyloid plaques in the brain (4). Interim results from the first 165 predromal and mild Alzheimer’s patients revealed that all doses of aducanumab drastically reduced levels of Aβ in the brain. It was discovered that those who took higher doses resulted in greater reductions, while no significant changes were present in the placebo group (4). Additionally, aducanumab appeared to slow the rate of cognitive decline. This was measured through clinical dementia rating sum of boxes (CDR-SB) and the mini-mental state examination (MMSE) (1).
Though Biogen also began two Phase 3 clinical trials to measure the efficacy of aducanumab, the trials were halted in March 2019 (5). However, later analysis based on additional follow-up data revealed that patients who had sufficient exposure to the medication showed major benefits. The findings were submitted to the FDA for approval of aducanumab treatment and granted priority review in August 2020 (1). Ultimately, Biogen’s clinical studies have provided a solid basis for further development in the treatment of Alzheimer’s.
Citations
(1) Laura Flavell P. Aducanumab [Internet]. Alzheimer's News Today. 2021 [cited 24
January 2021]. Available from: https://alzheimersnewstoday.com/aducanumab/
(2) Alzheimer's Disease Fact Sheet [Internet]. National Institute on Aging. 2021 [cited 24
January 2021]. Available from:
https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet
(3) Hardy J, Higgins G. Alzheimer's disease: the amyloid cascade hypothesis [Internet].
Go.gale.com. 2021 [cited 24 January 2021]. Available from: https://go.gale.com/ps/anonymous?id=GALE%7CA12207965&sid=googleScholar&v=2.1&it=r&linkaccess=abs&issn=00368075&p=AONE&sw=w>
(4) Multiple Dose Study of Aducanumab (BIIB037) (Recombinant, Fully Human Anti-Aβ
IgG1 mAb) in Participants With Prodromal or Mild Alzheimer's Disease - Full Text View - ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 24 January 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT01677572
(5) A Study of Aducanumab in Participants With Mild Cognitive Impairment Due to
Alzheimer's Disease or With Mild Alzheimer's Disease Dementia to Evaluate the Safety of Continued Dosing in Participants With Asymptomatic Amyloid-Related Imaging Abnormalities - Full Text View - ClinicalTrials.gov [Internet]. Clinicaltrials.gov. 2021 [cited 24 January 2021]. Available from: https://clinicaltrials.gov/ct2/show/NCT03639987?term=aducanumab&cond=Alzheimer+Disease