The great revolution against Alzheimer’s: ‘It’s the first time in human history that we’ve managed to slow the disease’ | Science
The fight against Alzheimer’s disease has entered a new era. The emergence of new drugs which slightly slow down its progression, as well as the discovery of biomarkers who open the way to early detection, has renewed the hope of attacking a condition that affects 50 million people in the world. After decades of setbacks and the inability to find effective treatments for dementia which destroys memory and individual autonomy, the scientific community looks with anticipation the diagnostic and pharmacological revolution in progress. A panel of experts has published a series of articles in Lancet Monday detailing these advances, while approaching the main controversy surrounding new treatments – the first to modify the course of the disease, but criticized to be expensive, have side effects and showing only modest efficiency.
Juan Fortea, leader of the Demention Neurobiology Group at the Sant Pau Research Institute and co-author of one of the Lancet Articles, indicates that Alzheimer’s search is a “paradigm change”. “We do not cure the disease,” he said, “but it is the first time in human history that we are talking about slowing down the progression of Alzheimer’s disease.”
The driving force behind this scientific turning point is a new generation of drugs that eliminate beta-amyloid proteins, which accumulate in the sick brain and the slow progression of the disease.
Albert Lleó, head of neurology in Sant Pau in Barcelona, underlines that this is only “the start of the trip”: “There are 138 additional drugs inquiry. These are the first to come. ”
Researchers also explore, for example, the potential of semaglutide, which has already revolutionized the treatment of obesity.
The drugs that have raised all hopes are called Lecanemab and Donanemab. In clinical trials, the first increase in the disease has slowed down the increase by 27% and the second of 35%. Both are approved in the United States and other countries, but the more conservative European Medicines Agency (EMA) has taken the time to approve LecaneMab (approving a year ago after having initially rejected it) and still examines Donanemab.
The two drugs were surrounded by controversy, even within the scientific community. First, due to the potential side effects – for example, Lecanemab was linked to brain hemorrhages and to the death of two patients – but also due to doubts about clinical benefit: what does reduce the increase in 27% disease for the daily life of a family? Other concerns include the price (estimated at around $ 25,000 per patient per year) and the fact that drugs are only intended for patients very specific at the first stages of the disease, with specific characteristics.
In the Lancet Series, the authors – some of whom have revealed conflicts of interest due to links with pharmaceutical societies producing these drugs – analyze this “range of reactions” and “skepticism” generated by these drugs in the scientific community, asking if the same thing would have happened with other diseases.
They even compare the efficiency, cost and impact of new Alzheimer’s drugs with those of other organic drugs for different conditions. For example, with Lecanemab and Donanemab, serious side effects occurred in 1 in 300 and 1 patients out of 65, respectively; But in the tests of Pembrolizumab (immunotherapy) for lung cancer, side effects occurred in 27% of cases. Another comparison: reducing the disability of anti-amyloid drugs in Alzheimer’s disease is similar to that observed in organic drug trials for rheumatoid arthritis or multiple sclerosis.
Based on the history of other biological drugs in different diseases, the authors maintain that the extent of the effect can be very similar. In these cases, they note, the prices were also high and the drugs were not free from side effects. Regarding the limited access to a very specific group of patients – experts estimate that for the moment, only 5% of people with Alzheimer will benefit from it – the authors emphasize that in multiple sclerosis, for example, the use of innovative drugs was limited to 36% of patients in 2017 and reached 74% in 2020.
“What these authors propose is not a direct comparison with other diseases, but rather a demonstration that there are other therapies in medicine which have a comparable effect, but Alzheimer has characteristics that undervalue these advances”, explains David Pérez, responsible for neurology at 12 of the Outabre in Madrid, which was not involved in this series. It refers to a handful of factors, ranging from scientific skepticism to social prejudices, which have created a climate conducive to controversy.
Pérez notes, for example, that the history of Alzheimer’s development of drugs has been “heyy”, marked by successive failures that have planted a seed of distrust in the scientific community. The controversy on Aducanumab, a drug approved in the United States in controversial circumstances but which failed commercially and was then removed by the manufacturer, did not help. “It was twisted in a twisted way, without clear advantage, which generated an atmosphere of distrust,” explains Pérez.
Nihilism and age
There is also “a lot of nihilism” surrounding this disease, “explains Lleó:” Several times, the diagnosis is not precisely made, and as there is no treatment, the public does not feel the need to demand a diagnosis or calendars as they do for a stroke or cancer. Sometimes the symptoms are considered a part of the normal development.
According to Pérez, another factor affecting the debate is age: “It is a disease that mainly affects the elderly, who cannot raise their voice and demand anything from society. These patients are a vulnerable group. ”
The extent of the disease, added experts, has also fueled doubts in terms of policy and regulation. “If it was not such a widespread disease, if it did not cause the pressure of the health system, costs and procedural changes, part of the controversy would not have been occurred. If it were a rare disease, we have no doubt that it would have been approved without any controversy and very quickly, “says Fortaa.
This first generation of drugs presents a challenge for health care systems. Both in the identification of patients who can benefit – which requires diagnostic tests and biomarkers to confirm the disease, as well as genetic studies to exclude incompatible mutations – and in treatment and monitoring itself: therapy is intravenous, administered in a day hospital, and requires regular MRI to monitor potential hemorrhages.
“Seeing patients in ambulatory consultations, once every six months or once a year is one thing; The treatment of Lecanemab is another. It involves infusions every two weeks in a day’s hospital, plus four MRI per year and many visits … A patient goes from one or two relatively short visits per year to 24, 30, or 35 visits. But because the workload represents. [initially] Include only a minority of patients, the system can gradually adapt, ”explains Fortaa.
Experts consulted emphasize that potential side effects are manageable. With regard to clinical advantages, Fortaa notes that “this 30% results in the patient who earns six months over 18 months”. In other words: “To go to the next phase, you progress 30% more slowly. You maintain more autonomy and quality of life because we slow down a disease that causes significant disability. We do not heal the disease. Patients are getting worse, but at a slower rate, ”he adds.
In an interview with El País, Cristina Maragall, president of the Pasqual Maragall Foundation, argued that for the scientific community and families, “it is essential that these drugs are starting to be used”.
Diagnostic Revolution
However, therapeutic advances are only part of this scientific transformation shaking the search for Alzheimer’s. The other pillar – Diagnosis – also progresses by step as a giant, in particular with the development of biomarkers who identify the biological traces of the disease never earlier. The authors believe that the arrival of plasma biomarkers, who detect traces of the disease in the blood – with a simple blood sample, such as a routine test, the biochemical signals of the disease can be identified – “will lead to a new diagnostic revolution.”
These tools are “crucial” to confirm the diagnosis at all stages of the disease, explains Fortaa. He explains that when clinical evaluation and neuropsychological tests confirm a slight cognitive impairment, in 60% of cases, it will be Alzheimer’s disease, but in the remaining 40%, it will not be; And depending on the situation, the patient’s progression and prognosis will be very different. “Therefore, I absolutely need a biomarker to identify who has Alzheimer’s disease. Otherwise, I won’t know what’s going on, ”he says. According to Fortaa, in asymptomatic contexts, the only way to select people who have Alzheimer’s disease will also be the biomarker. “The day there are preventive treatments, this biomarker will be our only tool to identify these people,” he adds.
Fortaa is very optimistic about MED’s advance advances: “We can now diagnose the presence of proteins [related to Alzheimer’s] In the brain of people in good cognitive health. We still cannot predict with certainty if or when all these people who have these proteins in their brain will develop the disease, and that is why the screening of the population is not recommended, but it is not science fiction. These are clinical trials that are underway and which will be published in 2027. In two years, we will know if the elimination of the amyloid in people without symptoms slows down the start of the disease. »»
If this is the case, he says, “performing the population and trying to prevent it would be justified.” “We are not there yet, but we have working tools that work and clinical trials.
Experts also predict more advances in the field of prevention. In fact, a scientific journal has identified 14 risk factors – in particular smoking, hypertension, sedentary lifestyle and pollution – to be avoided in order to prevent almost half of all cases of dementia. “There is potential in prevention,” says Eider Arenaza-Urquijo, Isglobal researcher and author of one of the articles in Lancet Series: “We have already seen a study that has shown that a lifestyle intervention – physical exercise, nutrition, cognitive and social activity – has an impact on the cognitive decline of people at higher risk of developing Alzheimer’s”, she says.
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