Alzheimer’s disease represents 70% of neurodegenerative diseases. This complex pathology is characterized by a slow but progressive evolution of cognitive faculties (memory, language, reasoning, attention), gradually reducing the autonomy of affected subjects. If its origin is multifactorial, researchers estimate that one in three cases could be avoided thanks to the adoption of a better lifestyle. In France, a million people are affected, mainly women. And, with the aging of the population, we anticipate a three-fold increase in the number of cases by 2050. There is therefore an urgent need to advance research. Especially since the only drugs available to date do not cure the disease but slow down the symptoms, with little improvement in the patient’s condition.
The arrival on the market of molecules with curative purposes therefore marks a turning point. On November 14, the European Medicines Agency authorized the marketing of lecanemab (Leqembi), from the Japanese laboratory Eisai and the American manufacturer Biogen. It is not yet distributed in France, but Eisai will submit a request for early access so that patients can benefit from it while the High Authority for Health issues its opinion on its marketing. The molecule can then be prescribed by specialists, particularly neurologists, in appropriate centers and services.
The pathology is manifested by the accumulation around neurons of plaques made up of abnormal proteins, beta-amyloid and tau, which alter the connection between neuronal cells, leading to their death. “The treatment uses immunotherapy: a monoclonal antibody, manufactured by genetic engineering, which targets amyloid plaques like a ballistic missile and destroys them. The objective is to stop the progressive process of the disease to allow the patient to regain an acceptable quality of life,” explains Dr Riadh Caïd-Essebsi, president of the medical council of the American Hospital of Paris.
“The objective is to stop the progression of the disease to restore the patient to an acceptable quality of life”
Very controlled access to treatment
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Administered intravenously every two weeks, lecanemab reduces the amyloid load by 70%. Exposing the risk of cerebral edema and hemorrhage which can be fatal, it is reserved for selected patients who have none, or only one copy, of the ApoE4 genetic variant, known to promote side effects. This risk is unfortunately common since only 5% to 15% of patients are eligible for treatment. The latter must undergo magnetic resonance imaging before starting Leqembi, as well as before taking the 5th, 7th and 14th doses, and at any time in the event of an alarming symptom to allow early detection of a lesion.
Other molecules in the future
With a similar mode of action, donanemab (Kisunla) is expected in 2025. The American laboratory Eli Lilly, which manufactures it, announces superior results to Leqembi. “We are entering a new pharmacological era with treatments which are still imperfect but make it possible to offer a solution to patients who are at the beginning of their illness. However, these immunotherapies are expensive. To see if the company is ready to bear the cost of this treatment, which amounts to 26,000 euros per year! » indicates Dr Caïd-Essebi. But research is progressing quickly. Molecules that target the tau protein are being studied. As are anti-obesity drugs, which prevent brain senescence by acting on inflammation. In the future, the solution will undoubtedly be a combination of treatments.
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