This article is the fourth installment in my series on Alzheimer’s disease. Read more about Alzheimer’s disease in part 1, part 2, and part 3 of the series.
The pharmaceutical and biotech companies, Eisai and Biogen recently revealed promising clinical trial results for a drug that could potentially treat Alzheimer’s disease.
In their clinical study, patients treated with the drug lecanemab experienced a 27% slower cognitive decline from Alzheimer’s disease than control groups. This treatment has been heralded as a breakthrough in Alzheimer’s disease research. Some scientists have cited the study as proof of one of the predominating theories of Alzheimer’s disease and its origins—the amyloid theory.
This leads us to two questions: what makes lecanemab unique and are these clinical trial results truly a historical breakthrough in Alzheimer’s research?
The biological origins of Alzheimer’s disease have puzzled scientists for decades. One of the leading theories of Alzheimer’s disease is the amyloid theory. Amyloid plaques are one of the biological indicators of Alzheimer’s disease progression and are caused by abnormal amyloid protein fragments. Amyloid fragments are typically soluble and can easily be cleared from the brain. However, sometimes these protein fragments become sticky and aggregate, forming dense plaques that the brain cannot remove. These plaques are hypothesized to induce cognitive decline in Alzheimer’s patients.
In recent years, several treatments have been developed to minimize the occurrence of amyloid plaques in the brain. Unfortunately, these treatments have had little to no effect on the cognitive decline seen in Alzheimer’s patients. Studies have also shown that Alzheimer’s patients can have a significant number of amyloid plaques without exhibiting any cognitive symptoms. This has caused a substantial amount of doubt within the scientific community that amyloid plaques are truly the cause of cognitive symptoms in Alzheimer’s patients.
Now, clinical results indicate that lecanemab has a different effect than other medications. Although lecanemab also targets amyloid in the brain, it seems to be effective at slowing the cognitive symptoms of Alzheimer’s disease. So, what makes lecanemab different?
One of the unique aspects of lecanemab is that it targets amyloid fibrils rather than amyloid plaques. Amyloid fibrils occur at an earlier stage of amyloid plaque formation and consist of much smaller clumps of amyloid protein. Researchers have suggested that lecanemab may be a more effective treatment for Alzheimer’s disease simply because it targets amyloid fibrils before they develop into amyloid plaques.
Others have speculated that the reason why lecanemab is effective at treating cognitive symptoms is not that it targets amyloid fibrils at all, but because one of the effects of lecanemab is that it increases levels of soluble amyloid in the brain.
Previous studies published by the University of Connecticut’s College of Medicine have shown that regardless of the buildup of amyloid plaques in the brain, people with higher levels of soluble amyloid were cognitively normal, while those with low levels of soluble amyloid experienced cognitive impairment. The team at the University of Connecticut has reasoned that the increase of soluble amyloid caused by lecanemab is what ultimately makes it an effective treatment for Alzheimer’s.
So, is lecanemab truly a historical breakthrough in Alzheimer’s disease research? While lecanemab seems to support the notion that amyloid plays a role in the origins of Alzheimer’s disease, it is still unclear whether these clinical trials alone support the amyloid plaque theory. Similarly, there still exist several limitations to the results of this clinical study.
A primary limitation is that this is an early-stage study with a limited number of participants. The difference in cognitive decline between Alzheimer’s patients taking lecanemab and the control group was statistically significant. However, by clinical standards this difference was relatively minimal. That is to say, some patients experienced a slower decline in cognitive abilities, but many did not. Additionally, the study was conducted for only eighteen months. Whether lecanemab will continue to be an effective treatment for a longer time and for a greater number of people is unknown.
A second limitation is that while lecanemab targets amyloid, there are other biomarkers and contributors to Alzheimer’s disease progression that the clinical study does not consider. For example, another significant biomarker for Alzheimer’s disease is tangles of tau protein in brain cells. These tau tangles are arguably more associated with cognitive symptoms than amyloid plaques, yet the clinical study of lecanemab does not take tau tangles into account. A contributor to Alzheimer’s disease progression is neuroinflammation which has been theorized as the main trigger for cognitive decline in Alzheimer’s patients. Without taking these aspects of Alzheimer’s disease into account, the results of the trial do not paint a full picture of the disease and its potential origins.
The final limitation of these clinical trial results is that the study was only conducted on Alzheimer’s patients with early or mild cognitive impairment. This means that the results of the study are not generalizable to all Alzheimer’s patients and may only help those who are in the early stages of the disease.
While lecanemab offers a beacon of hope for the development of effective Alzheimer’s disease treatments, there is still much more work to be done to understand precisely why lecanemab might be effective and what the origins of Alzheimer’s disease are. This clinical trial is a significant step in the right direction, but more information is needed before calling lecanemab a breakthrough in Alzheimer’s research.
As lecanemab is one of the few drugs made available to clinicians and to the public, it is likely to stir a significant market. However, whether lecanemab will be worth the risks and costs to individuals and to society remains an open question. Only time will tell.