2023-09-08 19:14:05
After decades of fruitless research, two new drugs are finally showing promise in tackling Alzheimer’s disease. The effectiveness of these drugs is such that they have even begun to be administered to asymptomatic people in the hope of further slowing the progression of the disease, or even preventing its appearance.
The first of these drugs, lecanémab (trade name Lequembi) manufactured by the companies Eisai and Biogen, received preliminary approval last January on the basis of positive results obtained during clinical trials carried out in people at the very beginning of the disease. who had mild cognitive impairment. These studies have shown that this drug slows the progression of Alzheimer’s by approximately 30%.
“Literally, lecanemab melts the amyloid plaques, and in a few months, the brains which were filled with amyloid are suddenly almost completely emptied of their content of this protein. The effect is spectacular,” describes Dr. Judes Poirier, professor in the Department of Psychiatry at McGill University and director of the Molecular Neurobiology Unit at the Douglas Research Center.
Building on these successes, the manufacturers decided to administer it to people who are still free of symptoms, but have a family history of Alzheimer’s and whose brain is already invaded by a certain number of amyloid plaques (a distinctive sign of the disease ). Of such clinical trials have therefore begun in the United States, Europe and Canada.
“We chose patients with well-established traces of the disease, but no symptoms yet. The objective is to delay the expression of the disease. It is assumed that we will slow the progression of the disease by more than 30% because we tackle it earlier in its development. And if this treatment makes it possible to delay the disease by five years, as is believed to happen, we would eliminate 50% of all cases of Alzheimer’s on the planet, quite simply because people will have time to die from other associated diseases. to aging before Alzheimer’s manifests itself”, affirms with hope Dr. Poirier, a leading Alzheimer’s specialist.
Lecanémab is a sort of vaccine composed of an antibody which attacks beta-amyloid, more particularly the polymerized form of this protein. Beta-amyloid is a molecule that is produced in excess in the brains of people with Alzheimer’s. The brain polymerizes these excess molecules, brings them together into small spheres and surrounds them with a layer of inflammatory cells which act as a waste bag. It then forms what we call amyloid plaques.
The second drug, donanemab, manufactured by the Eli Lilly company, is also an antibody that attacks an even more polymerized form of amyloid present inside senile plaques. Like lecanemab, it manages to eliminate many of the amyloid deposits within a few weeks. It slows down the disease by around 30 to 35%. The company presented these results at the international conference of the Alzheimer’s Association last July in Amsterdam, and subsequently submitted a complete file to the Food and Drug Administration (FDA) for approval.
The files for these two drugs have also been submitted to Health Canada. Dr. Poirier would be surprised that they are not approved for people who are early in the disease.
“The year of good news”
But these drugs do not cure people, “because amyloid is not the cause of Alzheimer’s. It is for this reason that the benefit is only a 30% reduction in disease progression. But as it is one of the important players in the biological process of the disease, it is clear that if we manage to [éliminer les plaques amyloïdes] before the symptoms arrive, it is likely that either they will not emerge, or they will emerge so much later that people will not suffer from the disease and will die from something else,” says Dr. Poirier .
Another major drawback is that lecanemab induces very strong immune responses in one in six patients. Some patients have small cerebrovascular accidents (CVA), others have cerebral edema which is problematic given that the brain is confined in the skull. These people must therefore be closely monitored by undergoing brain scans throughout the duration of treatment to detect these possible dangerous side effects.
What worries Dr. Poirier the most are these side effects that people who, initially, have no symptoms risk experiencing. “It’s a personal challenge, especially if you’re not sick. It’s not like you have cancer and you have nothing to lose,” he points out.
“This is the year of good news: we have two drugs, one is approved and another should be approved shortly. For the first time, we have succeeded in slowing down Alzheimer’s disease. And we are in the process of building the next prevention studies which, we hope, would make it possible to delay the disease by 5, or even 10 years, which means that we will no longer be talking regarding Alzheimer’s! » declares Dr. Poirier.
The researcher believes, however, that to get there, it will also be necessary to attack the tau protein, which, when found in the presence of amyloid, begins to polymerize and create toxic neurofibrillary tangles which accumulate in the neurons and suffocate them. “We are still too obsessed with amyloid alone. There are smaller companies, biotechs, which are starting to work on anti-tau vaccines. I am one of those who believe that it is necessary to remove the amyloid, but also the tau protein, to prevent them from meeting, because this meeting is one of the triggering factors for memory problems,” he explains.
However, very promising phase 2 human studies have shown that these vaccines are able to reduce the concentrations of tau protein in the brain. “A combination of the two might well become the most relevant solution for the prevention of Alzheimer’s! » says Dr. Poirier.
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