Alzheimer's disease has always threatened the health of tens of millions of elderly people around the world. Over the years, the development of its therapeutic drugs has also been very slow. Now, the emergence of a new drug has brought good news to patients with Alzheimer's disease.
On September 28, 2022, two pharmaceutical companies in the United States and Japan announced that the drug Lecanemab, jointly developed by them, has achieved good results in the Phase III clinical trial, becoming the first drug to clearly improve the symptoms of Alzheimer's disease [1].
Will this medicine be a light for patients with Alzheimer's disease? Let's talk about it in detail today.
As of now, Alzheimer's disease is still a chronic neurological disease that cannot be completely cured or even "reversed".
"Forgotten" (memory loss) is the most common symptom in patients with Alzheimer's disease. Because of this, this disease is always called " Alzheimer's " by the public - just like there is an "eraser" in the patient's mind.
In addition, as the course of the disease progresses, many patients will also experience strange tempers, suspicion, misunderstandings, or inconspicuous words, unwilling to communicate, and slow movements.
WHO Dr. Tedros D has said, "Alzheimer's disease has taken away the memory, independence and dignity of millions of people, and also the person we know and love."
According to statistics from the International Alzheimer's Disease Association, the total number of Alzheimer's disease patients worldwide is currently more than 50 million, and this number may rise to 139 million by 2050 [2].
Helplessly, what is the "eraser" in the mind of Alzheimer's patients? There is no conclusion in the medical community at present. There are only some related hypotheses, including: beta amyloid (Aβ) deposition hypothesis, Tau protein phosphorylation hypothesis, cholinergic hypothesis, vascular dysfunction hypothesis, inflammation hypothesis, etc., but the pathogenesis has not been fully elucidated.
Among all hypotheses, the most recognized hypothesis for many years is the beta amyloid deposition hypothesis. Preventing or clearing beta amyloid deposition is considered to be the most reliable therapeutic strategy and the main theoretical basis for the development of Alzheimer's disease drug.
In 2006, the University of Minnesota published a paper in the authoritative journal " Nature ", proving in a mouse model that Aβ*56, the subtype of Aβ, is neurotoxic and can lead to dementia in mice [3]. At that time, Nature even directly commented that Aβ*56 may be the "number one suspect" of Alzheimer's disease. The conclusion of
greatly consolidates the hypothesis of amyloid deposition of beta and allows research institutions and drug manufacturers from various countries to continue to increase their investment in this field. According to statistics, the paper has been cited nearly 2,300 times.
However, due to the numerous risk factors of disease and the lack of ideal animal models for drug development, large differences in clinical manifestations of patients, long courses of disease, and different intervention times, in recent decades, a large number of drug clinical trials targeting β amyloid have ended in failure.
In 2021, Matthew Schrager, a neurologist at Vanderbilt University in the United States, discovered that the experimental results pictures in many papers (including this article) of the author of the above-mentioned "Nature" paper have obvious cut and paste marks, and there is suspicion of fraud.
The authoritative journal Science conducted a six-month investigation to this end, and the evidence obtained also supported Schrager's suspicion. This seems to shake the "foundation" of the building that is β-amyloid hypothesis.
(A suggestive text has been added before the main text of the questioned paper: "The editor of this magazine has noticed the doubts about some pictures in this article, and is conducting relevant investigations and will make further responses as soon as possible. Readers should be cautious when citing relevant results." [3])
But in fact, what is questioned is not the β-amyloid hypothesis, but the relatively unpopular and special β-amyloid oligomer, Aβ*56.
Aβ has many monomeric fragments, the most studied include Aβ*42 and Aβ*40. Many Aβ-based monoclonal antibody drugs have performed well in clinical trials.
Professionals believe that even if the image confirmation and fraud in this paper have limited impact on related research, it still cannot shake the current mainstream status of the beta amyloid hypothesis. Although it is wrong to commit fraud, at the current stage when the pathogenesis is not clear, every exploration has its positive significance.
Doctors often use the CDR-SB scale when evaluating the effectiveness of early stages of Alzheimer's disease.
This scale involves six areas: memory, orientation, judgment and problem-solving ability, community affairs, housework and hobbies, and personal self-care ability. The sum of the scores in the six fields is the total score. The higher the score, the worse the cognitive performance and the more serious the degree of dementia.
This clinical trial involving 1795 patients showed that at month 18, the CDR-SB scores in the treatment group with the new drug Lecanemab were 27% lower than those in the placebo group, and the difference was statistically significant. In fact, at 6 months of treatment, the scores of the two had already changed significantly compared with baseline.
At the same time, other key secondary endpoints in the trial (such as changes in PET amyloid levels, AD evaluation scale-cognitive subscale 14, AD comprehensive score and AD collaborative study-Daily life ability scale for people with mild cognitive dysfunction, etc.) also achieved ideal results.
This indicates that the "effectiveness" results of this drug are relatively stable and credible. It is reported that the specific results of the clinical trial will be presented at the Alzheimer's disease conference in November 2022.
Beijing Brain Science and Brain-like Research Center Senior experts believe that if the data and papers officially released later support the current conclusions, it will show that Lecanemab is indeed helpful in slowing the course of disease in early stage patients with Alzheimer's disease.
This not only confirms the correlation between amyloid beta and Alzheimer's disease, but also suggests that the more soluble protofibrils appear in the formation of amyloid fibers are a more effective target. This is a major progress in drug research and development in this field.
In my country, there are about 10 million elderly patients with Alzheimer's disease aged 60 and above [4]. The increasing incidence and huge economic expenditure year by year have made Alzheimer's disease not only have a huge impact on the lives of patients and their families, but also increasingly become a major issue affecting public health and the sustainable development of society.
Deputy leader of the Neurology and Behavior Group of the Neurology Branch of the Chinese Medical Association and Department of Neurology, Huashan Hospital Affiliated to Fudan University, Professor Yu Jintai, believes that the results of Lecanemab's Phase III clinical trials undoubtedly gave a "heart-boosting injection" for the research and development of similar drugs.
The U.S. Food and Drug Administration (FDA) has accepted Lecanemab's application for biologics license under fast track certification and granted priority review rights. Relevant manufacturers said they will apply for approval in Japan and Europe.
Another phase III clinical trial of this drug is being carried out in my country at the same time, and the results are expected to be officially announced next year. In addition, some similar drugs from other companies have also shown good results in early clinical trials, and have been recognized by the FDA's breakthrough therapies. The subsequent progress is also worth looking forward to.
A new drug needs to go through a series of processes such as approval, marketing, and procurement before it can finally meet the patient. This takes some time.
We hope that all parties in society can pay more and more attention to and support the group of Alzheimer's disease patients, and we also believe that as time goes by, the treatment drugs and strategies for Alzheimer's disease will become more and more accurate and efficient.
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