DEC 03, 2022 9:00 AM PST

Steps to Curing Alzheimer's: Lecanemab

WRITTEN BY: Greta Anne

Every day, we come closer to finding a cure for Alzheimer's. Recently, the New England Journal of Medicine published an article about a drug named "lecanemab." This drug could potentially slow down the progression of Alzheimer's.1

Before we get into all that, let's quickly recap what Alzheimer's even is. Alzheimer's is a disease that impairs the brain's ability to carry out simple tasks and even causes dementia. Dementia is the byproduct of a decline in cognitive function. Alzheimer's affects the brain via toxic proteins that build up, stop neuron function, and ultimately die. These proteins are called amyloid plaques and tau tangles.2 See video below about Alzheimer's effects on the brain.

To reiterate, amyloid plaques and tau tangles build up in the brain and lead to a loss of ability to perform daily tasks, personality changes, memory loss, and more. Soluble amyloid-beta-peptide oligomer, is the full name of one of the toxic proteins involved in Alzheimer’s.3 So, if Alzheimer's is the RESULT of a buildup of toxic proteins, could we potentially block their formation and stop Alzheimer's? 

YES!

That's where lecanemab comes in. Lecanemab is a humanized monoclonal antibody ("mab") that binds to amyloid-beta protofibrils. Twelve months into a dose-finding study with upwards of 800 Alzheimer's disease participants showed no difference between lecanemab and placebo; however, the data at 18 months has further insight. In the 18-month analyses, there was a dose and time-dependent clearance of amyloid with lecanemab and it was associated with less clinical decline in some cases. This study measured amyloid levels before and after administration of lecanemab, and the data showed an overall reduction of amyloid-beta. Additionally, being associated with less clinical decline means that people on lecanemab had less cognitive decline.

So what's the catch? 

Keep in mind this study only has 18 months of published data (despite additional trials being conducted.) Amyloid-related imaging abnormalities, also known as ARIA, are a side effect of decreasing amyloid-beta.4 A type of ARIA, ARIA-E, is usually detectable by increased signal intensities when imaging various parts of the brain. It is also associated with symptoms of headache, confusion, gait difficulties, and visual disturbances.5 Another type of ARIA is ARIA-H, which is detectable by via cerebral microhemorrhages (mH), small hemorrhages on the brain.5 As great as lecanemab sounds in the context of Alzheimer's, there is an incidence of ARIA-E (12.6%) ARIA-H (17.3%) in lecanemab, compared to placebo of ARIA-E (9.9%), ARIA-H (10.7%). There is also an increased incidence of brain bleeds in patients taking lecanemab (17%) compared to placebo (9%) and a dropout rate of 17.2%.1

Lecanemab is a reasonably promising drug and a huge step in the direction of curing Alzheimer's. There are a few limitations with tolerability, with a drop out rate of 17.2%, and a plethora of side effects. However, this is undoubtedly a monumental trial in Alzheimer's research, and it will be exciting to see what is next!

 

References 

1 van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, L., Cohen, S., Froelich, L., Katayama, S., Sabbagh, M., Vellas, B., Watson, D., Dhadda, S., Irizarry, M., Kramer, L. D., & Iwatsubo, T. (2022). Lecanemab in Early Alzheimer's Disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2212948 

2 National Institute of Aging, 2021. https://www.nia.nih.gov/health 

3 Lublin, A. L., & Gandy, S. (2010). Amyloid‐β Oligomers: Possible Roles as Key Neurotoxins in Alzheimer's Disease. Mount Sinai Journal of Medicine: A Journal of Translational and Personalized Medicine: A Journal of Translational and Personalized Medicine, 77(1), 43-49. Chicago 

4 Shi M, Chu F, Zhu F, Zhu J. Impact of Anti-amyloid-β Monoclonal Antibodies on the Pathology and Clinical Profile of Alzheimer's Disease: A Focus on Aducanumab and Lecanemab. Front Aging Neurosci. 2022;14:870517. Published 2022 Apr 12. doi:10.3389/fnagi.2022.870517 

5 Sperling RA, Jack CR Jr, Black SE, et al. Amyloid-related imaging abnormalities in amyloid-modifying therapeutic trials: recommendations from the Alzheimer's Association Research Roundtable Workgroup. Alzheimers Dement. 2011;7(4):367-385. doi:10.1016/j.jalz.2011.05.2351 

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